Serotonergic Mechanisms as Targets for Existing and Novel Antipsychotics

  • Herbert Y. MeltzerEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 212)


A variety of serotonin (5-HT) receptors, especially 5-HT2A, 5-HT1A, 5-HT6, 5-HT7, and 5-HT2C, have been postulated to contribute to the mechanism of action of atypical antipsychotic drugs (APDs), i.e., APDs which cause fewer extrapyramidal side effects (EPS) at clinically optimal doses, in contrast with typical APDs, which are more likely to cause EPS. This advantage, rarely disputed, has made such drugs the preferred treatment for schizophrenia and other indications for APDs. These 5-HT receptors are still of interest as components of novel multireceptor or stand-alone APDs, and potentially to remediate cognitive deficits in schizophrenia. Almost all currently available atypical APDs are 5-HT2A receptor inverse agonists, as well as dopamine (DA) D2 receptor antagonists or partial agonists. Amisulpride, an exceptional atypical APD, has 5-HT7 antagonism to complement its DA D2/3 antagonism. Some atypical APDs are also 5-HT1A partial agonists, 5-HT6, or 5-HT7 antagonists, or some combination of the above. 5-HT2C antagonism has been found to contribute to the metabolic side effects of some atypical APDs, whereas 5-HT2C agonists have potential as stand-alone APDs and/or cognitive enhancers. This review will provide an update of current preclinical and clinical evidence for the role of these five 5-HT receptors in the actions of current APDs and for the development of novel psychotropic drugs.


Serotonin Dopamine Glutamate GABA Antipsychotic Schizophrenia Hallucinations Memory Phencyclidine 



Supported, in part, by donations from Mr. and Mrs. Robert Weisman and Mr. and Mrs. Edward Hintz.


  1. Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL (2009) Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. Psychopharmacology (Berl) 205(1):119–128CrossRefGoogle Scholar
  2. Abi-Dargham A, Van de Giessen E, Slifstein M, Kegeles LS, Laruelle M (2009) Baseline and amphetamine-stimulated dopamine activity are related in drug-naïve schizophrenic subjects. Biol Psychiatry 65(12):1091–1093PubMedCrossRefGoogle Scholar
  3. Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36(4–5):589–599PubMedCrossRefGoogle Scholar
  4. Albizu L, Holloway T, González-Maeso J, Sealfon SC (2011) Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 61(4):770–777PubMedCrossRefGoogle Scholar
  5. Altar CA, Wasley AM, Neale RF, Stone GA (1986) Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 16(4):517–525PubMedCrossRefGoogle Scholar
  6. Andrade R (2011) Serotonergic regulation of neuronal excitability in the prefrontal cortex. Neuropharmacology 61(3):382–386PubMedCrossRefGoogle Scholar
  7. Andree TH, Mikuni M, Tong CY, Koenig JI, Meltzer HY (1986) Differential effect of subchronic treatment with various neuroleptic agents on serotonin 2 receptors in rat cerebral cortex. J Neurochem 46(1):191–197PubMedCrossRefGoogle Scholar
  8. Araneda R, Andrade R (1991) 5-Hydroxytryptamine 2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience 40(2):399–412PubMedCrossRefGoogle Scholar
  9. Argo TR, Carnahan RM, Perry PJ (2004) Aripiprazole, a novel atypical antipsychotic drug. Pharmacotherapy 24(2):212–228PubMedCrossRefGoogle Scholar
  10. Arnt J, Bang-Andersen B, Grayson B, Bymaster FP, Cohen MP, DeLapp NW, Giethlen B, Kreilgaard M, McKinzie DL, Neill JC, Nelson DL, Nielsen SM, Poulsen MN, Schaus JM, Witten LM (2010) Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol 13(8):1021–1033PubMedCrossRefGoogle Scholar
  11. Arnt J, Olsen CK (2011) 5-HT6 receptor ligands and their antipsychotic potential. Int Rev Neurobiol 96:141–161PubMedCrossRefGoogle Scholar
  12. Arnt J, Skarsfeldt T (1998) Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology 18:63–101PubMedCrossRefGoogle Scholar
  13. Assié MB, Ravailhe V, Faucillon V, Newman-Tancredi A (2005) Contrasting contribution of 5-hydroxytryptamine 1a receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain. J Pharmacol Exp Ther 315(1):265–272CrossRefGoogle Scholar
  14. Bantick RA, Deakin JF, Grasby PM (2001) The 5-HT1A receptor in schizophrenia: a promising target for novel atypical neuroleptics? J Psychopharmacol 15(1):37–46PubMedCrossRefGoogle Scholar
  15. Barker EL, Westphal RS, Schmidt D, Sanders-Bush E (1994) Constitutively active 5-hydroxytryptamine2C receptors reveal novel inverse agonist activity of receptor ligands. J Biol Chem 269(16):11687–11690PubMedGoogle Scholar
  16. Bays HE (2009) Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for ‘sick fat’ and metabolic disease. Expert Rev Cardiovasc Ther 7(11):1429–1445PubMedCrossRefGoogle Scholar
  17. Boast C, Bartolomeo AC, Morris H, Moyer JA (1999) 5HT antagonists attenuate MK801-impaired radial arm maze performance in rats. Neurobiol Learn Mem 71(3):259–271PubMedCrossRefGoogle Scholar
  18. Boess FG, Monsma FJ Jr, Sleight AJ (1998) Identification of residues in transmembrane regions III and VI that contribute to the ligand binding site of the serotonin 5-HT6 receptor. J Neurochem 71(5):2169–2177PubMedCrossRefGoogle Scholar
  19. Bonaccorso S, Meltzer HY, Li Z, Dai J, Alboszta AR, Ichikawa J (2002) SR46349-B, a 5-HT (2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology 27:430–441PubMedCrossRefGoogle Scholar
  20. Bortolozzi A, Diaz-Mataix L, Scorza MC, Celada P, Artigas F (2005) The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem 95:1597–1607PubMedCrossRefGoogle Scholar
  21. Bruins Slot LA, Lestienne F, Grevoz-Barret C, Newman-Tancredi A, Cussac D (2009) F15063, a potential antipsychotic with dopamine D(2)/D(3) receptor antagonist and 5-HT(1A) receptor agonist properties: influence on immediate-early gene expression in rat prefrontal cortex and striatum. Eur J Pharmacol 620(1–3):27–35PubMedCrossRefGoogle Scholar
  22. Buckley P, Thompson P, Way L, Meltzer HY (1994) Substance abuse among patients with treatment-resistant schizophrenia: characteristics and implications for clozapine therapy. Am J Psychiatry 151(3):385–389PubMedGoogle Scholar
  23. Burnet PW, Eastwood SL, Harrison PJ (1996) 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 15(5):442–455PubMedCrossRefGoogle Scholar
  24. Butini S, Gemma S, Campiani G et al (2009) Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior. J Med Chem 52(1):151–169PubMedCrossRefGoogle Scholar
  25. Calcagno E, Carli M, Baviera M, Invernizzi RW (2009) Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockade. J Neurochem 108:521–532PubMedCrossRefGoogle Scholar
  26. Canal CE, Olaghere da Silva UB, Gresch PJ, Watt EE, Sanders-Bush E, Airey DC (2010) The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology (Berl) 209(2):163–174CrossRefGoogle Scholar
  27. Carr DB, Cooper DC, Ulrich SL, Spruston N, Surmeier DJ (2002) Serotonin receptor activation inhibits sodium current and dendritic excitability in prefrontal cortex via a protein kinase C-dependent mechanism. J Neurosci 22(16):6846–6855PubMedGoogle Scholar
  28. Cartmell J, Monn JA, Schoepp DD (1999) The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J Pharmacol Exp Ther 291(1):161–170PubMedGoogle Scholar
  29. Casey DE, Sands EE, Heisterberg J, Yang HM (2008) Efficacy and safety of bifeprunox in patients with an acute exacerbation of schizophrenia: results from a randomized, double-blind, placebo-controlled, multicenter, dose-finding study. Psychopharmacology (Berl) 200(3):317–331CrossRefGoogle Scholar
  30. Chen ML, Tsai TC, Wang LK, Lin YY, Tsai YM, Lee MC, Tsai FM (2012) Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-α-directed cell apoptosis in neutrophils. Int Immunopharmacol 12(1):197–204PubMedCrossRefGoogle Scholar
  31. Choi YK, Snigdha S, Shahid M, Neill JC, Tarazi FI (2009) Subchronic effects of phencyclidine on dopamine and serotonin receptors: implications for schizophrenia. J Mol Neurosci 38(3):227–235PubMedCrossRefGoogle Scholar
  32. Chung YC, Li Z, Dai J, Meltzer HY, Ichikawa J (2004) Clozapine increases both acetylcholine and dopamine release in rat ventral hippocampus: role of 5-HT1A receptor agonism. Brain Res 1023:54–63PubMedCrossRefGoogle Scholar
  33. Coyle JT, Tsai G (2004) NMDA receptor function, neuroplasticity, and the pathophysiology of schizophrenia. Int Rev Neurobiol 59:491–515PubMedCrossRefGoogle Scholar
  34. Creed-Carson M, Oraha A, Nobrega JN (2011) Effects of 5-HT(2A) and 5-HT(2C) receptor antagonists on acute and chronic dyskinetic effects induced by haloperidol in rats. Behav Brain Res 219(2):273–279PubMedCrossRefGoogle Scholar
  35. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I (2008) Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol 594(1–3):32–38PubMedCrossRefGoogle Scholar
  36. Da Silva Costa-Aze V, Quiedeville A, Boulouard M, Dauphin F (2012) 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice. Psychopharmacology (Berl) 222(1):99–115CrossRefGoogle Scholar
  37. de Bruin NM, Prickaerts J, van Loevezijn A, Venhorst J, de Groote L, Houba P, Reneerkens O, Akkerman S, Kruse CG (2011) Two novel 5-HT6 receptor antagonists ameliorate scopolamine-induced memory deficits in the object recognition and object location tasks in Wistar rats. Neurobiol Learn Mem 96(2):392–402PubMedCrossRefGoogle Scholar
  38. De Deurwaerdère P, Navailles S, Berg KA, Clarke WP, Spampinato U (2004) Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens. J Neurosci 24(13):3235–3241PubMedCrossRefGoogle Scholar
  39. De Deurwaerdère P, Spampinato U (1999) Role of serotonin(2A) and serotonin(2B/2C) receptor subtypes in the control of accumbal and striatal dopamine release elicited in vivo by dorsal raphe nucleus electrical stimulation. J Neurochem 73(3):1033–1042PubMedCrossRefGoogle Scholar
  40. Delille HK, Becker JM, Burkhardt S, Bleher B, Terstappen GC, Schmidt M, Meyer AH, Unger L, Marek GJ, Mezler M (2012) Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology 62(7):2184–2191PubMedCrossRefGoogle Scholar
  41. Depoortère R, Auclair AL, Bardin L, Bruins Slot L, Kleven MS, Colpaert F, Vacher B, Newman-Tancredi A (2007) F15063, a compound with D2/D3 antagonist, 5-HT1A agonist and D4 partial agonist properties III. Activity in models of cognition and negative symptoms. Br J Pharmacol 151(2):266–277PubMedCrossRefGoogle Scholar
  42. Depoortere R, Boulay D, Perrault G, Bergis O, Decobert M, Françon D, Jung M, Simiand J, Soubrié P, Scatton B (2003) SSR181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist II: behavioral profile predictive of an atypical antipsychotic activity. Neuropsychopharmacology 28(11):1889–1902PubMedCrossRefGoogle Scholar
  43. Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (1999) SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system. Neuropharmacology 38(8):1195–1205PubMedCrossRefGoogle Scholar
  44. Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (1998) Selective blockade of serotonin2C/2B receptors enhances dopamine release in the rat nucleus accumbens. Neuropharmacology 37(2):265–272PubMedCrossRefGoogle Scholar
  45. Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 25(47):10831–10843PubMedCrossRefGoogle Scholar
  46. Doherty MD, Pickel VM (2000) Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area. Brain Res 864(2):176–185PubMedCrossRefGoogle Scholar
  47. Dougherty JP, Aloyo VJ (2011) Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice. Psychopharmacology (Berl) 215(3):581–593CrossRefGoogle Scholar
  48. Dunlop J, Sabb AL, Mazandarani H, Zhang J, Kalgaonker S, Shukhina E, Sukoff S, Vogel RL, Stack G, Schechter L, Harrison BL, Rosenzweig-Lipson S (2005) WAY-163909 [(7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole], a novel 5-hydroxytryptamine 2C receptor-selective agonist with anorectic activity. J Pharmacol Exp Ther 313(2):862–869PubMedCrossRefGoogle Scholar
  49. Egashira N, Ishigami N, Mishima K, Iwasaki K, Oishi R, Fujiwara M (2008) Delta9-tetrahydrocannabinol-induced cognitive deficits are reversed by olanzapine but not haloperidol in rats. Prog Neuropsychopharmacol Biol Psychiatry 32(2):499–506PubMedCrossRefGoogle Scholar
  50. Elvander-Tottie E, Eriksson TM, Sandin J, Ogren SO (2009) 5-HT(1A) and NMDA receptors interact in the rat medial septum and modulate hippocampal-dependent spatial learning. Hippocampus 19(12):1187–1198PubMedCrossRefGoogle Scholar
  51. Fribourg M, Moreno JL, Holloway T, Provasi D, Baki L, Mahajan R, Park G, Adney SK, Hatcher C, Eltit JM, Ruta JD, Albizu L, Li Z, Umali A, Shim J, Fabiato A, MacKerell AD Jr, Brezina V, Sealfon SC, Filizola M, González-Maeso J, Logothetis DE (2011) Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 147(5):1011–1023PubMedCrossRefGoogle Scholar
  52. Galici R, Boggs JD, Miller KL, Bonaventure P, Atack JR (2008) Effects of SB-269970, a 5-HT7 receptor antagonist, in mouse models predictive of antipsychotic-like activity. Behav Pharmacol 19(2):153–159PubMedCrossRefGoogle Scholar
  53. Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, Veinbergs I, Dyssegaard A, Brunmark P, Tabatabaei A, Davis RE, Brann MR, Hacksell U, Bonhaus DW (2007) ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental models. J Pharmacol Exp Ther 322(2):862–870PubMedCrossRefGoogle Scholar
  54. Garzya V, Forbes IT, Gribble AD, Hadley MS, Lightfoot AP, Payne AH, Smith AB, Douglas SE, Cooper DG, Stansfield IG, Meeson M, Dodds EE, Jones DN, Wood M, Reavill C, Scorer CA, Worby A, Riley G, Eddershaw P, Ioannou C, Donati D, Hagan JJ, Ratti EA (2006) Studies towards the identification of a new generation of atypical antipsychotic agents. Bioorg Med Chem Lett 17(2):400–405PubMedCrossRefGoogle Scholar
  55. Gewirtz JC, Marek GJ (2000) Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology 23(5):569–576PubMedCrossRefGoogle Scholar
  56. Ginovart N, Kapur S (2012) Role of dopamine D2 receptors for antipsychotic activity. In: Gross G, Geyer MA (eds) Current antipsychotics, vol 212. Handbook of Experimental Pharmacology. Springer, BerlinGoogle Scholar
  57. Gleason SD, Shannon HE (1997) Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice. Psychopharmacology 129:79–84PubMedCrossRefGoogle Scholar
  58. Goldman-Rakic PS, Selemon LD (1997) Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr Bull 23(3):437–458PubMedCrossRefGoogle Scholar
  59. González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452(7183):93–97PubMedCrossRefGoogle Scholar
  60. Gozzi A, Crestan V, Turrini G, Clemens M, Bifone A (2010) Antagonism at serotonin 5-HT(2A) receptors modulates functional activity of frontohippocampal circuit. Psychopharmacology (Berl) 209(1):37–50CrossRefGoogle Scholar
  61. Gravius A, Laszy J, Pietraszek M, Sághy K, Nagel J, Chambon C, Wegener N, Valastro B, Danysz W, Gyertyán I (2011) Effects of 5-HT6 antagonists, Ro-4368554 and SB-258585, in tests used for the detection of cognitive enhancement and antipsychotic-like activity. Behav Pharmacol 22(2):122–135PubMedCrossRefGoogle Scholar
  62. Gray JA, Roth BL (2007) Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophr Bull 33(5):1100–1119PubMedCrossRefGoogle Scholar
  63. Gründer G, Hippius H, Carlsson A (2009) The ‘atypicality’ of antipsychotics: a concept re-examined and re-defined. Nat Rev Drug Discov 8(3):197–202PubMedCrossRefGoogle Scholar
  64. Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC (1989) Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci USA 86(24):9762–9976PubMedCrossRefGoogle Scholar
  65. Grauer SM, Graf R, Navarra R, Sung A, Logue SF, Stack G, Huselton C, Liu Z, Comery TA, Marquis KL, Rosenzweig-Lipson S (2009) WAY-163909, a 5-HT2C agonist, enhances the preclinical potency of current antipsychotics. Psychopharmacology (Berl) 204(1):37–48CrossRefGoogle Scholar
  66. Grayson BI, Idris NF, Neill JC (2007) Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat. Behav Brain Res 184(1):31–38PubMedCrossRefGoogle Scholar
  67. Gronier B (2008) Involvement of glutamate neurotransmission and N-methyl-d-aspartate receptor in the activation of midbrain dopamine neurons by 5-HT1A receptor agonists: an electrophysiological study in the rat. Neuroscience 156(4):995–1004PubMedCrossRefGoogle Scholar
  68. Gross G, Drescher K (2012) The role of dopamine D3 receptors in antipsychotic activity and cognitive functions. In: Geyer M, Gross G (eds) Novel antischizophrenia treatments; Handbook of Experimental Pharmacology, vol 213. Springer, HeidelbergGoogle Scholar
  69. Gu Z, Jiang Q, Yan Z (2007) RGS4 modulates serotonin signaling in prefrontal cortex and links to serotonin dysfunction in a rat model of schizophrenia. Mol Pharmacol 71(4):1030–1039PubMedCrossRefGoogle Scholar
  70. Gyertyán I, Kiss B, Sághy K, Laszy J, Szabó G, Szabados T, Gémesi LI, Pásztor G, Zájer-Balázs M, Kapás M, Csongor EÁ, Domány G, Tihanyi K, Szombathelyi Z (2011) Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents. Neurochem Int 59(6):925–935PubMedCrossRefGoogle Scholar
  71. Hagiwara H, Fujita Y, Ishima T, Kunitachi S, Shirayama Y, Iyo M, Hashimoto K (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone: role of serotonin 5-HT1A receptors. Eur Neuropsychopharmacol 18(6):448–454PubMedCrossRefGoogle Scholar
  72. Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY (1993) Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 34:702–712PubMedCrossRefGoogle Scholar
  73. Hahn A, Wadsak W, Windischberger C, Baldinger P, Höflich AS, Losak J, Nics L, Philippe C, Kranz GS, Kraus C, Mitterhauser M, Karanikas G, Kasper S, Lanzenberger R (2012) Differential modulation of the default mode network via serotonin-1A receptors. Proc Natl Acad Sci USA 109(7):2619–2624PubMedCrossRefGoogle Scholar
  74. Hashimoto K, Fujita Y, Shimizu E, Iyo M (2005) Phencyclidine-induced cognitive deficits in mice are improved by subsequent sub-chronic administration of clozapine, but not haloperidol. Eur J Pharmacol 519:114–117PubMedCrossRefGoogle Scholar
  75. Hedlund PB (2009) The 5-HT7 receptor and disorders of the nervous system: an overview. Psychopharmacology (Berl) 206(3):345–354CrossRefGoogle Scholar
  76. Hedlund PB, Sutcliffe JG (2004) Functional, molecular and pharmacological advances in 5-HT7 receptor research. Trends Pharmacol Sci 25(9):481–486PubMedCrossRefGoogle Scholar
  77. Henry SA, Lehmann-Masten V, Gasparini F, Geyer MA, Markou A (2002) The mGLUR5 antagonist MPEP, but not the mGLUR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity. Neuropharmacology 43:1199–1209PubMedCrossRefGoogle Scholar
  78. Herrick-Davis K, Grinde E, Teitler M (2000) Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther 295(1):226–232PubMedGoogle Scholar
  79. Homan EJ, Copinga S, Elfström L (1998) 2-aminotetralin-derived substituted benzamides with mixed dopamine D2, D3, and serotonin 5-HT1A receptor binding properties: a novel class of potential atypical antipsychotic agents. Bioorg Med Chem 6(11):2111–2126PubMedCrossRefGoogle Scholar
  80. Horiguchi M, Huang M, Meltzer HY (2011a) The role of 5-hydroxytryptamine 7 receptors in the phencyclidine-induced novel object recognition deficit in rats. J Pharmacol Exp Ther 338(2):605–614PubMedCrossRefGoogle Scholar
  81. Horiguchi M, Huang M, Meltzer HY (2011b) Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats. Psychopharmacology (Berl) 217(1):13–24CrossRefGoogle Scholar
  82. Horiguchi M, Meltzer HY (2012) The role of 5-HT(1A) receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats. Psychopharmacology (Berl) 221(2):205–215CrossRefGoogle Scholar
  83. Horisawa T, Ishibashi T, Nishikawa H, Enomoto T, Toma S, Ishiyama T, Taiji M (2011) The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone. Behav Brain Res 220(1):83–90PubMedCrossRefGoogle Scholar
  84. Howes OD, Kapur S (2009) The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull 35(3):549–562PubMedCrossRefGoogle Scholar
  85. Hoyer D, Pazos A, Probst A, Palacios JM (1986) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376(1):97–107PubMedCrossRefGoogle Scholar
  86. Huang M, Dai J, Meltzer HY (2011) 5-HT(2A) and 5-HT(2C) receptor stimulation are differentially involved in the cortical dopamine efflux-studied in 5-HT(2A) and 5-HT(2C) genetic mutant mice. Eur J Pharmacol 652(1–3):40–45PubMedCrossRefGoogle Scholar
  87. Huang M, Horiguchi M, Felix AR, Meltzer HY (2012) 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux. Neuroreport 23(7):436–440PubMedGoogle Scholar
  88. Hurlemann R, Matusch A, Kuhn KU, Berning J, Elmenhorst D, Winz O, Kolsch H, Zilles K, Wagner M, Maier W, Bauer A (2008) A 5-HT2A receptor density is decreased in the at-risk mental state. Psychopharmacology (Berl) 195(4):579–590CrossRefGoogle Scholar
  89. Ichikawa J, Meltzer HY (1992) The effect of chronic atypical antipsychotic drugs and haloperidol on amphetamine-induced dopamine release in vivo. Brain Res 574(1–2):98–104PubMedCrossRefGoogle Scholar
  90. Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY (2001) 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76(5):1521–1531PubMedCrossRefGoogle Scholar
  91. Ichikawa J, Li Z, Dai J, Meltzer HY (2002a) Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1A receptor agonism. Brain Res 956(2):349–357PubMedCrossRefGoogle Scholar
  92. Ichikawa J, Dai J, O’Laughlin IA, Dai J, Fowler W, Meltzer HY (2002b) Atypical, but not typical, antipsychotic drugs selectively increase acetylcholine release in rat medial prefrontal cortex, nucleus accumbens and striatum. Neuropsychopharmacology 26(3):325–339PubMedCrossRefGoogle Scholar
  93. Ikemoto K, Nishimura A, Okado N, Mikuni M, Nishi K, Nagatsu I (2000) Human midbrain dopamine neurons express serotonin 2A receptor: an immunohistochemical demonstration. Brain Res 853(2):377–380PubMedCrossRefGoogle Scholar
  94. Ishibashi T, Horisawa T, Tokuda K, Ishiyama T, Ogasa M, Tagashira R, Matsumoto K, Nishikawa H, Ueda Y, Toma S, Oki H, Tanno N, Saji I, Ito A, Ohno Y, Nakamura M (2010) Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther 334(1):171–181PubMedCrossRefGoogle Scholar
  95. Ishikane T, Kusumi I, Matsubara R, Matsubara S, Koyama T (1997) Effects of serotonergic agents on the up-regulation of dopamine D2 receptors induced by haloperidol in rat striatum. Eur J Pharmacol 321:163–169PubMedCrossRefGoogle Scholar
  96. Issa G, Wilson C, Terry AV Jr, Pillai A (2010) An inverse relationship between cortisol and BDNF levels in schizophrenia: data from human postmortem and animal studies. Neurobiol Dis 39(3):327–333PubMedCrossRefGoogle Scholar
  97. Jakab RL, Goldman-Rakic PS (1998) 5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci USA 95:735–740PubMedCrossRefGoogle Scholar
  98. Kalkman HO, Subramanian N, Hoyer D (2001) Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders. Neuropsychopharmacology 25(6):904–914PubMedCrossRefGoogle Scholar
  99. Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45:789–796PubMedCrossRefGoogle Scholar
  100. Karasawa J, Hashimoto K, Chaki S (2008) D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats. Behav Brain Res 186(1):78–83PubMedCrossRefGoogle Scholar
  101. Kargieman L, Riga MS, Artigas F, Celada P (2012) Clozapine reverses phencyclidine-induced desynchronization of prefrontal cortex through a 5-HT(1A) receptor-dependent mechanism. Neuropsychopharmacology 37(3):723–733PubMedCrossRefGoogle Scholar
  102. Kehne JH, Baron BM, Carr AA, Chaney SF, Elands J, Feldman DJ, Frank RA, van Giersbergen PL, McCloskey TC, Johnson MP, McCarty DR, Poirot M, Senyah Y, Siegel BW, Widmaier C (1996) Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile. J Pharmacol Exp Ther 277(2):968–981PubMedGoogle Scholar
  103. Kimura K, Nomikos GG, Svensson TH (1993) Effects of amperozide on psychostimulant-induced hyperlocomotion and dopamine release in the nucleus accumbens. Pharmacol Biochem Behav 44(1):27–36PubMedCrossRefGoogle Scholar
  104. Kiss B, Horváth A, Némethy Z, Schmidt E, Laszlovszky I, Bugovics G, Fazekas K, Hornok K, Orosz S, Gyertyán I, Agai-Csongor E, Domány G, Tihanyi K, Adham N, Szombathelyi Z (2010) Cariprazine (RGH-188), a dopamine D3 receptor-preferring, D3/D2 dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther 333:328–340PubMedCrossRefGoogle Scholar
  105. Kleven MS, Barret-Grévoz C, Bruins Slot L, Newman-Tancredi A (2005) Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology 49(2):135–143PubMedCrossRefGoogle Scholar
  106. Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW (1996) Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem 66(1):47–56PubMedCrossRefGoogle Scholar
  107. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A (1996) Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol 317:417–423PubMedCrossRefGoogle Scholar
  108. Kozikowski AP, Cho SJ, Jensen NH, Allen JA, Svennebring AM, Roth BL (2010) HTS and rational drug design to generate a class of 5-HT(2C)-selective ligands for possible use in schizophrenia. ChemMedChem 5(8):1221–1225PubMedCrossRefGoogle Scholar
  109. Kruzich PJ, See RE (2000) An evaluation of the role of 5-HT(2) receptor antagonism during subchronic antipsychotic drug administration in rats. Brain Res 875(1–2):35–43PubMedCrossRefGoogle Scholar
  110. Kuroki T, Meltzer HY, Ichikawa J (1999) Effect of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther 288(2):774–781PubMedGoogle Scholar
  111. Laruelle M (1998) Imaging dopamine transmission in schizophrenia. A review and meta-analysis. A review and meta-analysis. Q J Nucl Med 42(3):211–221PubMedGoogle Scholar
  112. Leggio GM, Cathala A, Neny M, Rouge-Pont F, Drago F, Piazza PV, Spampinato U (2009) In vivo evidence that constitutive activity of serotonin2C receptors in the medial prefrontal cortex participates in the control of dopamine release in the rat nucleus accumbens: differential effects of inverse agonist versus antagonist. J Neurochem 111(2):614–623PubMedCrossRefGoogle Scholar
  113. Leng A, Ouagazzal A, Feldon J, Higgins GA (2003) Effect of the 5-HT6 receptor antagonists Ro04-6790 and Ro65-7199 on latent inhibition and prepulse inhibition in the rat: comparison to clozapine. Pharmacol Biochem Behav 75(2):281–288PubMedCrossRefGoogle Scholar
  114. Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6(4):312–324PubMedCrossRefGoogle Scholar
  115. Leysen JE, Van Gompel P, Gommeren W, Woestenborghs R, Janssen PA (1986) Down regulation of serotonin-S2 receptor sites in rat brain by chronic treatment with the serotonin-S2 antagonists: ritanserin and setoperone. Psychopharmacology (Berl) 188(4):434–444Google Scholar
  116. Li Z, AJ, Ichikawa J, Dai J, and Meltzer HY (2005) 5-HT2a and 5-HT2c receptor antagonism enhances risperidone-induced dopamine (DA) efflux in rat medial prefrontal cortex (mPFC) and diminishes it in the nucleus accumbens (NAC). Neurosci Abs 914.10Google Scholar
  117. Li Z, Ichikawa J, Huang M, Prus AJ, Dai J, Meltzer HY (2005) ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Psychopharmacology (Berl) 183(2):144–153CrossRefGoogle Scholar
  118. Liegeois J-F, Ichikawa J, Meltzer HY (2002) 5HT2A receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner. Brain Res 947:157–165PubMedCrossRefGoogle Scholar
  119. Liem-Moolenaar M, Rad M, Zamuner S, Cohen AF, Lemme F, Franson KL, van Gerven JM, Pich EM (2011) Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men. Br J Clin Pharmacol 71(6):907–916PubMedCrossRefGoogle Scholar
  120. Linck VM, Bessa MM, Herrmann AP, Iwu MM, Okunji CO, Elisabetsky E (2012) 5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine. Prog Neuropsychopharmacol Biol Psychiatry 36(1):29–33PubMedCrossRefGoogle Scholar
  121. Lladó-Pelfort L, Santana N, Ghisi V, Artigas F, Celada P (2012) 5-HT1A Receptor agonists 1304 enhance pyramidal cell firing in prefrontal cortex through a preferential action on GABA 1305 interneurons. Cereb Cortex 22(7):1487–1497PubMedCrossRefGoogle Scholar
  122. Marek GJ, Wright RA, Schoepp DD, Monn JA, Aghajanian GK (2000) Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 292(1):76–87PubMedGoogle Scholar
  123. Martin CK, Redman LM, Zhang J, Sanchez M, Anderson CM, Smith SR, Ravussin E (2011) Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab 96(3):837–845PubMedCrossRefGoogle Scholar
  124. Martín-Cora FJ, Pazos A (2004) Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species. Br J Pharmacol 141(1):92–104PubMedCrossRefGoogle Scholar
  125. Martin P, Waters N, Carlsson A, Carlsson ML (1997) The apparent antipsychotic action of the 5-HT2A receptor antagonist M100907 in a mouse model of schizophrenia is counteracted by ritanserin. J Neural Transm 104(4–5):561–564PubMedCrossRefGoogle Scholar
  126. Marazziti D, Baroni S, Catena Dell’Osso M, Bordi F, Borsini F (2011) Serotonin receptors of type 6 (5-HT6): what can we expect from them? Curr Med Chem 18(18):2783–2790PubMedCrossRefGoogle Scholar
  127. Margolese HC, Chouinard G, Kolivakis TT, Beauclair L, Miller R (2005a) Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction. Can J Psychiatry 50(9):541–547PubMedGoogle Scholar
  128. Margolese HC, Chouinard G, Kolivakis TT, Beauclair L, Miller R, Annable (2005b) Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: incidence and management strategies in patients with schizophrenia. Can J Psychiatry 50(11):703–714PubMedGoogle Scholar
  129. Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105(4–5):365–396PubMedCrossRefGoogle Scholar
  130. Marquis KL, Sabb AL, Logue SF, Brennan JA, Piesla MJ, Comery TA, Grauer SM, Ashby CR Jr, Nguyen HQ, Dawson LA, Barrett JE, Stack G, Meltzer HY, Harrison BL, Rosenzweig-Lipson S (2007) WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]: a novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity. J Pharmacol Exp Ther 320(1):486–496PubMedCrossRefGoogle Scholar
  131. Matsubara S, Meltzer HY (1989) Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex. Life Sci 45(15):1397–1406PubMedCrossRefGoogle Scholar
  132. Matsumoto I, Inoue Y, Iwazaki T, Pavey G, Dean B (2005) 5-HT2A and muscarinic receptors in schizophrenia: a postmortem study. Neurosci Lett 379(3):164–168PubMedCrossRefGoogle Scholar
  133. Matsumoto M, Shikanai H, Togashi H, Izumi T, Kitta T, Hirata R, Yamaguchi T, Yoshioka M (2008) Characterization of clozapine-induced changes in synaptic plasticity in the hippocampal-mPFC pathway of anesthetized rats. Brain Res 1195:50–55PubMedCrossRefGoogle Scholar
  134. McLean SL, Idris NF, Woolley ML, Neill JC (2009) D(1)-like receptor activation improves PCP-induced cognitive deficits in animal models: implications for mechanisms of improved cognitive function in schizophrenia. Eur Neuropsychopharmacol 19(6):440–450PubMedCrossRefGoogle Scholar
  135. McLean SL, Neill JC, Idris NF, Marston HM, Wong EH, Shahid M (2010) Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat. Behav Brain Res 214(2):240–247PubMedCrossRefGoogle Scholar
  136. McMahon LR, Filip M, Cunningham KA (2001) Differential regulation of the mesoaccumbens circuit by serotonin 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Neurosci 21(19):7781–7787PubMedGoogle Scholar
  137. McMillen BA, Jones EA, Hill LJ, Williams HL, Björk A, Myers RD (1993) Amperozide, a 5-HT2 antagonist, attenuates craving for cocaine by rats. Pharmacol Biochem Behav 46(1):125–129PubMedCrossRefGoogle Scholar
  138. Meltzer HY (1989) Duration of a clozapine trial in neuroleptic-resistant schizophrenia. Arch Gen Psychiatry 46(7):672PubMedCrossRefGoogle Scholar
  139. Meltzer HY (1993) New drugs for the treatment of schizophrenia. Psychiatr Clin North Am 16(2):365–385PubMedGoogle Scholar
  140. Meltzer HY, Arvanitis L, Bauer D, Rein W, Meta-Trial Study Group (2004) Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry 161(6):975–984PubMedCrossRefGoogle Scholar
  141. Meltzer HY, Elkis H, Vanover IK, Weiner DM, van Kammen DP, Peters P, Hacksell U (2012) Pimavanserin,a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone 2 mg/day but does not enhance eficacy of haloperidol 2 mg/day: comparison with reference dose risperidone, 6 mg/day. Schizr Res (in press)Google Scholar
  142. Meltzer HY, Horiguchi M, Massey BW (2011) The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment. Psychopharmacology (Berl) 213(2–3):289–305CrossRefGoogle Scholar
  143. Meltzer HY, Huang M (2008) In vivo actions of atypical antipsychotic drug on serotonergic and dopaminergic systems. Prog Brain Res 172:177–197PubMedCrossRefGoogle Scholar
  144. Meltzer HY, Li Z, Kaneda Y, Ichikawa J (2003) Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27(7):1159–1172PubMedCrossRefGoogle Scholar
  145. Meltzer HY, Massey BW, Horiguchi M (2012) Serotonin receptors as targets for drugs useful to treat psychosis and cognitive impairment in schizophrenia. Curr Pharm Biotechnol 13(8):1572–86Google Scholar
  146. Meltzer HY, Matsubara S, Lee JC (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D1, D2, and serotonin2 pKi values. J Pharmacol Exp Ther 251:238–246PubMedGoogle Scholar
  147. Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233–255PubMedCrossRefGoogle Scholar
  148. Meltzer HY, Mills R, Revell S, Williams H, Johnson A, Bahr D, Friedman JH (2010) Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacology 35(4):881–892PubMedCrossRefGoogle Scholar
  149. Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: a review. Schizophr Bull 2(1):19–76PubMedGoogle Scholar
  150. Meneses A (2004) Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task. Behav Brain Res 155(2):275–282PubMedCrossRefGoogle Scholar
  151. Meneses A, Perez-Garcia G (2007) 5-HT(1A) receptors and memory. Neurosci Biobehav Rev 31(5):705–727PubMedCrossRefGoogle Scholar
  152. Meyer U, Knuesel I, Nyffeler M, Feldon J (2010) Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis. Psychopharmacology (Berl) 208(4):531–534CrossRefGoogle Scholar
  153. Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ, Dubois B, Geyer MA, Goodwin GM, Gorwood P, Jay TM, Joëls M, Mansuy IM, Meyer-Lindenberg A, Murphy D, Rolls E, Saletu B, Spedding M, Sweeney J, Whittington M, Young LJ (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11(2):141–168PubMedCrossRefGoogle Scholar
  154. Millan MJ, Brocco M, Gobert A, Joly F, Bervoets K, Rivet JM, Newman-Tancredi A, Audinot V, Maurel S (1999) Contrasting mechanisms of action and sensitivity to antipsychotics of phencyclidine versus amphetamine: importance of nucleus accumbens 5-HT2A site for PCP-induced locomotion in the rat. Eur J Neurosci 11:4419–4432PubMedCrossRefGoogle Scholar
  155. Miyamoto S, Duncan GE, Marx CE, Lieberman JA (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10(1):79–104PubMedCrossRefGoogle Scholar
  156. Monsma FJ Jr, Shen Y, Ward RP, Hamblin MW, Sibley DR (1993) Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 43(3):320–332PubMedGoogle Scholar
  157. Moreno JL, Kurita M, Holloway T, López J, Cadagan R, Martínez-Sobrido L, García-Sastre A, González-Maeso J (2011) Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT2A and mGlu2 receptors in the adult offspring. J Neurosci 31(5):1863–1872PubMedCrossRefGoogle Scholar
  158. Mössner R, Lesch KP (1998) Role of serotonin in the immune system and in neuroimmune interactions. Brain Behav Immun 12(4):249–271PubMedCrossRefGoogle Scholar
  159. Nagai T, Murai R, Matsui K, Kamei H, Noda Y, Furukawa H, Nabeshima T (2009) Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. Psychopharmacology (Berl) 202(1–3):315–328CrossRefGoogle Scholar
  160. Nawa H, Takei N (2006) Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 56(1):2–13PubMedCrossRefGoogle Scholar
  161. Neill JC, Barnes S, Cook S, Grayson B, Idris NF, McLean SL, Snigdha S, Rajagopal L, Harte MK (2010) Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol Ther 128(3):419–432PubMedCrossRefGoogle Scholar
  162. Newman-Tancredi A (2010) The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. Curr Opin Investig Drugs 11(7):802–812PubMedGoogle Scholar
  163. Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verrièle L, Audinot V, Millan MJ (1998) Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol 355(2–3):245–256PubMedCrossRefGoogle Scholar
  164. Nguyen QT, Schroeder LF, Mank M, Muller A, Taylor P, Griesbeck O, Kleinfeld D (2010) An in vivo biosensor for neurotransmitter release and in situ receptor activity. Nat Neurosci 13(1):127–132PubMedCrossRefGoogle Scholar
  165. Nichols CD (2009) Serotonin 5-HT(2A) receptor function as a contributing factor to both neuropsychiatric and cardiovascular diseases. Cardiovasc Psychiatry Neurol 2009:475108PubMedGoogle Scholar
  166. Ohno Y, Imaki J, Mae Y, Takahashi T, Tatara A (2011) Serotonergic modulation of extrapyramidal motor disorders in mice and rats: role of striatal 5-HT3 and 5-HT6 receptors. Neuropharmacology 60(2–3):201–208PubMedCrossRefGoogle Scholar
  167. Oka M, Noda Y, Ochi Y, Furukawa K, Une T, Kurumiya S, Hino K, Karasawa T (1993) Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties. J Pharmacol Exp Ther 264(1):158–165PubMedGoogle Scholar
  168. O’Neil RT, Emeson RB (2012) Quantitative analysis of 5HT(2C) receptor RNA editing patterns in psychiatric disorders. Neurobiol Dis 45(1):8–13PubMedGoogle Scholar
  169. Parada MA, Hernandez L, Puig de Parada M, Rada P, Murzi E (1997) Selective action of acute systemic clozapine on acetylcholine release in the rat prefrontal cortex by reference to the nucleus accumbens and striatum. J Pharmacol Exp Ther 281:582–588PubMedGoogle Scholar
  170. Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 13(9):1102–1107PubMedCrossRefGoogle Scholar
  171. Pitsikas N, Zisopoulou S, Pappas I, Sakellaridis N (2008) The selective 5-HT(6) receptor antagonist Ro 04-6790 attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801. Behav Brain Res 188(2):304–309PubMedCrossRefGoogle Scholar
  172. Plassat JL, Amlaiky N, Hen R (1993) Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol 44(2):229–236PubMedGoogle Scholar
  173. Pouzet B, Didriksen M, Arnt J (2002) Effects of the 5-HT(7) receptor antagonist SB-258741 in animal models for schizophrenia. Pharmacol Biochem Behav 71(4):655–665PubMedCrossRefGoogle Scholar
  174. Prinssen EP, Colpaert FC, Koek W (2002) 5-HT1A receptor activation and anti-cataleptic effects: high-efficacy agonists maximally inhibit haloperidol-induced catalepsy. Eur J Pharmacol 453(2–3):217–221PubMedCrossRefGoogle Scholar
  175. Puig MV, Gulledge AT (2011) Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol 44(3):449–464PubMedCrossRefGoogle Scholar
  176. Rasmussen H, Ebdrup BH, Erritzoe D, Aggernaes B, Oranje B, Kalbitzer J, Pinborg LH, Baaré WF, Svarer C, Lublin H, Knudsen GM, Glenthoj B (2011) Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine. Psychopharmacology (Berl) 213(2–3):583–592CrossRefGoogle Scholar
  177. Rauser L, Savage JE, Meltzer HY, Roth BL (2001) Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor. J Pharmacol Exp Ther 299(1):83–89PubMedGoogle Scholar
  178. Reavill C, Kettle A, Holland V, Riley G, Blackburn T (1999) Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist. Br J Pharmacol 126(3):572–574PubMedCrossRefGoogle Scholar
  179. Richelson E, Souder T (2000) Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci 68(1):29–39PubMedCrossRefGoogle Scholar
  180. Richtand NM, Welge JA, Logue AD, Keck PE Jr, Strakowski SM, McNamara RK (2008) Role of serotonin and dopamine receptor binding in antipsychotic efficacy. Prog Brain Res 172:155–175PubMedCrossRefGoogle Scholar
  181. Riemer C, Borroni E, Levet-Trafit B, Martin JR, Poli S, Porter RH, Bös M (2003) Influence of the 5-HT6 receptor on acetylcholine release in the cortex: pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a potent and selective 5-HT6 receptor antagonist. J Med Chem 46(7):1273–1276PubMedCrossRefGoogle Scholar
  182. Rinaldi-Carmona M, Congy C, Santucci V, Simiand J, Gautret B, Neliat G, Labeeuw B, Le Fur G, Soubrié PG, Breliere JC (1992) Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonists. J Pharmacol Exp Ther 262:759–768PubMedGoogle Scholar
  183. Rollema H, Lu Y, Schmidt AW, Zorn SH (1997) Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. Eur J Pharmacol 338:R3–R5PubMedCrossRefGoogle Scholar
  184. Roth BL, Ciaranello RD, Meltzer HY (1992) Binding of typical and atypical antipsychotic agents to transiently expressed 5-HT1C receptors. J Pharmacol Exp Ther 260:1361–1365PubMedGoogle Scholar
  185. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR (1994) Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 268(3):1403–1410PubMedGoogle Scholar
  186. Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY (1995) D4 Dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology (Berl) 120(3):365–368CrossRefGoogle Scholar
  187. Salvador R, Sarró S, Gomar JJ, Ortiz-Gil J, Vila F, Capdevila A, Bullmore E, McKenna PJ, Pomarol-Clotet E (2010) Overall brain connectivity maps show cortico-subcortical abnormalities in schizophrenia. Hum Brain Mapp 31(12):2003–2014PubMedCrossRefGoogle Scholar
  188. Schmidt CJ, Sorensen SM, Kehne JH, Carr AA, Palfreyman MG (1995) The role of 5-HT2A receptors in antipsychotic activity. Life Sci 56:2209–2222PubMedCrossRefGoogle Scholar
  189. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 124:57–73PubMedCrossRefGoogle Scholar
  190. Scorza MC, Castañé A, Bortolozzi A, Artigas F (2010) Clozapine does not require 5-HT1A receptors to block the locomotor hyperactivity induced by MK-801 Clz and MK-801 in KO1A mice. Neuropharmacology 59(1–2):112–120PubMedCrossRefGoogle Scholar
  191. Semenova S, Geyer MA, Sutcliffe JG, Markou A, Hedlund PB (2008) Inactivation of the 5-HT(7) receptor partially blocks phencyclidine-induced disruption of prepulse inhibition. Biol Psychiatry 63(1):98–105PubMedCrossRefGoogle Scholar
  192. Shahid M, Walker GB, Zorn SH, Wong EH (2009) Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol 23(1):65–73PubMedCrossRefGoogle Scholar
  193. Shin EJ, Whang WK, Kim S, Bach JH, Kim JM, Nguyen XK, Nguyen TT, Jung BD, Yamada K, Nabeshima T, Kim HC (2010) Parishin C attenuates phencyclidine-induced schizophrenia-like psychosis in mice: involvements of 5-HT1A receptor. J Pharmacol Sci 113(4):404–408PubMedCrossRefGoogle Scholar
  194. Shirazi-Southall S, Rodriguez DE, Nomikos GG (2002) Effects of typical and atypical antipsychotics and receptor selective compounds on acetylcholine efflux in the hippocampus of the rat. Neuropsychopharmacology 26(5):583–594PubMedCrossRefGoogle Scholar
  195. Silva MT, Calil HM (1975) Screening hallucinogenic drugs: systematic study of three behavioral tests. Psychopharmacologia 42(2):163–171PubMedCrossRefGoogle Scholar
  196. Sipes TE, Geyer MA (1995) DOI disruption of prepulse inhibition of startle in the rat is mediated by 5-HT2A and not 5-HT2C receptors. Behav Pharmacol 6:839–842PubMedCrossRefGoogle Scholar
  197. Sipes TE, Geyer MA (1997) DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum. Brain Res 761:97–104PubMedCrossRefGoogle Scholar
  198. Snigdha S, Horiguchi M, Huang M, Li Z, Shahid M, Neill JC, Meltzer HY (2010) Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 332(2):622–631PubMedCrossRefGoogle Scholar
  199. Somerville EM, Horwood JM, Lee MD, Kennett GA, Clifton PG (2007) 5-HT(2C) receptor activation inhibits appetitive and consummatory components of feeding and increases brain c-fos immunoreactivity in mice. Eur J Neurosci 25(10):3115–3124PubMedCrossRefGoogle Scholar
  200. Souza RP, de Luca V, Meltzer HY, Lieberman JA, Kennedy JL (2010) Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia. Pharmacogenet Genomics 20(4):274–276PubMedGoogle Scholar
  201. Steward LJ, Kennedy MD, Morris BJ, Pratt JA (2004) The atypical antipsychotic drug clozapine enhances chronic PCP-induced regulation of prefrontal cortex 5-HT2A receptors. Neuropharmacology 47(4):527–537PubMedCrossRefGoogle Scholar
  202. Strange PG (2001) Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev 53(1):119–133PubMedGoogle Scholar
  203. Sumiyoshi T, Matsui M, Yamashita I, Nohara S, Uehara T, Kurachi M, Meltzer HY (2000) Effect of adjunctive treatment with serotonin-1A agonist tandospirone on memory functions in schizophrenia. J Clin Psychopharmacol 20(3):386–388PubMedCrossRefGoogle Scholar
  204. Sumiyoshi T, Matsui M, Nohara S, Yamashita I, Kurachi M, Sumiyoshi C, Jayathilake K, Meltzer HY (2001a) Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry 158(10):1722–1725PubMedCrossRefGoogle Scholar
  205. Sumiyoshi T, Matsui M, Yamashita I, Nohara S, Kurachi M, Uehara T, Sumiyoshi S, Sumiyoshi C, Meltzer HY (2001b) The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia. Biol Psychiatry 49(10):861–868PubMedCrossRefGoogle Scholar
  206. Sumiyoshi T, Bubenikova-Valesova V, Horacek J, Bert B (2008) Serotonin1A Receptors in the pathophysiology of schizophrenia: development of novel cognition-enhancing therapeutics. Adv Ther 25:1037–1056PubMedCrossRefGoogle Scholar
  207. Swainston Harrison T, Perry CM (2004) Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs 64(15):1715–1736PubMedCrossRefGoogle Scholar
  208. Swanson CJ, Schoepp DD (2002) The group II metabotropic glutamate receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0]-hexane-4,6-dicarboxylate (LY379268) and clozapine reverse phencyclidine-induced behaviors in monoamine-depleted rats. J Pharmacol Exp Ther 303:919–927PubMedCrossRefGoogle Scholar
  209. Tanaka H, Tatsuno T, Shimizu H, Hirose A, Kumasaka Y, Nakamura M (1995) Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain. Gen Pharmacol 26(8):1765–1772PubMedCrossRefGoogle Scholar
  210. Tanibuchi Y, Fujita Y, Kohno M, Ishima T, Takatsu Y, Iyo M, Hashimoto K (2009) Effects of quetiapine on phencyclidine-induced cognitive deficits in mice: a possible role of alpha1-adrenoceptors. Eur Neuropsychopharmacol 19(12):861–867PubMedCrossRefGoogle Scholar
  211. Thomas DR, Hagan JJ (2004) 5-HT7 receptors. Curr Drug Targets CNS Neurol Disord 3(1):81–90PubMedCrossRefGoogle Scholar
  212. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O’Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS (1998) Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr 178:440–466PubMedGoogle Scholar
  213. Ukai W, Ozawa H, Tateno M, Hashimoto E, Saito T (2004) Neurotoxic potential of haloperidol in comparison with risperidone: implication of Akt-mediated signal changes by haloperidol. J Neural Transm 111(6):667–681PubMedCrossRefGoogle Scholar
  214. Uslaner JM, Smith SM, Huszar SL, Pachmerhiwala R, Hinchliffe RM, Vardigan JD, Hutson PH (2009) Combined administration of an mGlu2/3 receptor agonist and a 5-HT 2A receptor antagonist markedly attenuate the psychomotor-activating and neurochemical effects of psychostimulants. Psychopharmacology (Berl) 206(4):641–651CrossRefGoogle Scholar
  215. Vaidya VA, Marek GJ, Aghajanian GK, Duman RS (1997) 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J Neurosci 17(8):2785–2795PubMedGoogle Scholar
  216. Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, Del Tredici AL, Piu F, Schiffer HH, Ott TR, Burstein ES, Uldam AK, Thygesen MB, Schlienger N, Andersson CM, Son TY, Harvey SC, Powell SB, Geyer MA, Tolf BR, Brann MR, Davis RE (2006) Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 317(2):910–918PubMedCrossRefGoogle Scholar
  217. Varty GB, Bakshi VP, Geyer MA (1999) M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in Sprague-Dawley and Wistar rats. Neuropsychopharmacology 20:311–321PubMedCrossRefGoogle Scholar
  218. Vauquelin G, Bostoen S, Vanderheyden P, Seeman P (2012) Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism. Naunyn Schmiedebergs Arch Pharmacol 385(4):337–372PubMedCrossRefGoogle Scholar
  219. Vázquez-Borsetti P, Celada P, Cortés R, Artigas F (2011) Simultaneous projections from prefrontal cortex to dopaminergic and serotonergic nuclei. Int J Neuropsychopharmacol 14(3):289–302PubMedCrossRefGoogle Scholar
  220. Volavka J (2012) Clozapine is gold standard, but questions remain. Int J Neuropsychopharmacol 4:1–4Google Scholar
  221. Volk DW, Lewis DA (2010) Prefrontal cortical circuits in schizophrenia. Curr Top Behav Neurosci 4:485–508PubMedCrossRefGoogle Scholar
  222. Vysokanov A, FloresHernandez J, Surmeier DJ (1998) mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons. Neurosci Lett 258(3):179–182PubMedCrossRefGoogle Scholar
  223. Wadenberg ML (1992) Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH 23390 in the rat. J Neural Transm Gen Sect 89:49–59PubMedCrossRefGoogle Scholar
  224. Wadenberg ML, Hicks PB, Richter JT, Young KA (1998) Enhancement of antipsychoticlike properties of raclopride in rats using the selective serotonin2A receptor antagonist MDL 100,907. Biol Psychiatry 44(6):508–515PubMedCrossRefGoogle Scholar
  225. Wagner M, Quednow BB, Westheide J, Schlaepfer TE, Maier W, Kühn KU (2005) Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride. Neuropsychopharmacology 30(2):381–390PubMedCrossRefGoogle Scholar
  226. Wallace TL, Porter RH (2011) Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease. Biochem Pharmacol 82(8):891–903PubMedCrossRefGoogle Scholar
  227. Wang RY, Liang X (1995) M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine-induced blockade of NMDA responses in pyramidal neurons of the rat medial prefrontal cortical slice. Neuropsychopharmacology 19(1):74–85CrossRefGoogle Scholar
  228. Wang L, Mamah D, Harms MP, Karnik M, Price JL, Gado MH, Thompson PA, Barch DM, Miller MI, Csernansky JG (2008) Progressive deformation of deep brain nuclei and hippocampal-amygdala formation in schizophrenia. Biol Psychiatry 64(12):1060–1068PubMedCrossRefGoogle Scholar
  229. Ward RP, Hamblin MW, Lachowicz JE, Hoffman BJ, Sibley DR, Dorsa DM (1995) Localization of serotonin subtype 6 receptor messenger RNA in the rat brain by in situ hybridization histochemistry. Neuroscience 64(4):1105–1111PubMedCrossRefGoogle Scholar
  230. Waters KA, Stean TO, Hammond B, Virley DJ, Upton N, Kew JN, Hussain I (2011) Effects of the selective 5-HT(7) receptor antagonist SB-269970 in animal models of psychosis and cognition. Behav Brain Res 228(1):211–218PubMedCrossRefGoogle Scholar
  231. Watson DJ, Marsden CA, Millan MJ, Fone KC (2012) (2 012). Blockade of dopamine D3 but not D2 receptors reverses the novel object discrimination impairment produced by post-weaning social isolation: implications for schizophrenia and its treatment. Int J Neuropsychopharmacol 15(4):471–484PubMedCrossRefGoogle Scholar
  232. Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR (2001) 5-hydroxytryptamine2A receptor inverse agonists as antipsychotics. J Pharmacol Exp Ther 299:268–276PubMedGoogle Scholar
  233. Wiesel FA, Nordström AL, Farde L, Eriksson B (1994) An open clinical and biochemical study of ritanserin in acute patients with schizophrenia. Psychopharmacology (Berl) 114(1):31–38CrossRefGoogle Scholar
  234. Willins DL, Meltzer HY (1997) Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther 282(2):699–706PubMedGoogle Scholar
  235. Winklbaur B, Ebner N, Sachs G, Thau K, Fischer G (2006) Substance abuse in patients with schizophrenia. Dialogues Clin Neurosci 8(1):37–43PubMedGoogle Scholar
  236. Woodward ND, Purdon SE, Meltzer HY, Zald DH (2005) A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol 8(3):457–472PubMedCrossRefGoogle Scholar
  237. Yadav PN, Kroeze WK, Farrell MS, Roth BL (2011) Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo. J Pharmacol Exp Ther 339(1):99–105PubMedCrossRefGoogle Scholar
  238. Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T (2008) Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain 10:1–6Google Scholar
  239. Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (2008) Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency. J Pharmacol Exp Ther 327(2):316–323PubMedCrossRefGoogle Scholar
  240. Yuen EY, Jiang Q, Chen P, Feng J, Yan Z (2008) Activation of 5-HT2A/C receptors counteracts 5-HT1A regulation of n-methyl-D-aspartate receptor channels in pyramidal neurons of prefrontal cortex. J Biol Chem 283(25):17194–17204PubMedCrossRefGoogle Scholar
  241. Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z (2005) Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J Neurosci 25(23):5488–5501PubMedCrossRefGoogle Scholar
  242. Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z (2012) The novel antipsychotic drug lurasidone enhances N-methyl-D-aspartate receptor-mediated synaptic responses. Mol Pharmacol 81(2):113–119PubMedCrossRefGoogle Scholar
  243. Zajdel P, Marciniec K, Maślankiewicz A, Satała G, Duszyńska B, Bojarski AJ, Partyka A, Jastrzębska-Więsek M, Wróbel D, Wesołowska A, Pawłowski M (2012) Quinoline- and isoquinoline-sulfonamide derivatives of LCAP as potent CNS multi-receptor-5-HT1A/5-HT2A/5-HT7 and D2/D3/D4-agents: the synthesis and pharmacological evaluation. Bioorg Med Chem 20(4):1545–1556PubMedCrossRefGoogle Scholar
  244. Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J (2006) Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Biochem Pharmacol 71(4):521–529PubMedCrossRefGoogle Scholar
  245. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (2005) Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol: a double-blind and randomized study. Psychopharmacology (Berl) 178(1):35–40CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Psychiatry and Behavioral SciencesNorthwestern Feinberg School of MedicineChicagoUSA

Personalised recommendations