Interactions of Hallucinogens with the Glutamatergic System: Permissive Network Effects Mediated Through Cortical Layer V Pyramidal Neurons

Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 36)

Abstract

Recordings made from layer V (L5) pyramidal cells of the prefrontal cortex (PFC) and neocortex in rodent slice preparations have shown that serotonin (5-hydroxytryptamine, 5-HT) and serotonergic hallucinogens induce an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the apical dendritic field by activating 5-HT2A receptors. Serotonergic hallucinogens induce late EPSCs and increase recurrent network activity when subcortical or mid-cortical regions are stimulated at low frequencies (e.g., 0.1 Hz). A range of agonists or positive allosteric modulators (PAMs) for mostly Gi/o-coupled receptors, including metabotropic glutamate2 (mGlu2), adenosine A1, or μ-opioid receptors, suppress these effects of 5-HT2A receptor stimulation. Furthermore, a range of mostly Gq/11-coupled receptors (including orexin2 [OX2]; α1-adrenergic, and mGlu5 receptors) similarly induce glutamate (Glu) release onto L5 pyramidal cells. Evidence implicates a number of brain regions in mediating these effects of serotonergic hallucinogens and Gq/11-coupled receptors including the midline and intralaminar thalamic nuclei, claustrum, and neurons in deep PFC. These effects on 5-HT2A receptors and related GPCRs appear to play a major role in the behavioral effects of serotonergic hallucinogens, such as head twitches in rodents and higher order behaviors such as rodent lever pressing on the differential-reinforcement-of-low rate 72-s (DRL 72-s) schedule. This implies that the effects of 5-HT2A receptor activation on the activity of L5 pyramidal cells may be responsible for mediating a range of behaviors linked to limbic circuitry with connectivity between the PFC, striatum, thalamus, claustrum, striatum, amygdala, and the hippocampal formation.

Keywords

In vitro electrophysiology Layer V pyramidal neurons DOI-induced head-twitch response DRL 72-s behavior 

References

  1. Aghajanian GK (2009) Modeling “psychosis” in vitro by inducing disordered neuronal network activity in cortical brain slices. Psychopharmacology 206:575–585PubMedPubMedCentralGoogle Scholar
  2. Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36(3/4):589–599Google Scholar
  3. Ardayfio PA et al (2008) The 5-hydroxytryptamine2A receptor antagonist R-(+)-a-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) attenuates impulsivity after both drug-induced disruption (dizocilpine) and enhancement (antidepressant drugs) of differential-reinforcement-of-low-rate 72-s behavior in the rat. J Pharmacol Exp Ther 327:891–897PubMedGoogle Scholar
  4. Avesar D, Gulledge AT (2012) Selective serotonergic excitation of callosal projection neurons. Front Neural circuits 6Google Scholar
  5. Ballanger B et al (2010) Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 67:416–421PubMedGoogle Scholar
  6. Barre A et al (2012) Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning. Proc Natl Acad Sci USA 113:E1382–E1391Google Scholar
  7. Beique J-C et al (2007) Mechanism of the 5-hydroxytryptamine2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc Natl Acad Sci USA 104:9870–9875PubMedPubMedCentralGoogle Scholar
  8. Benneyworth MA et al (2007) A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol Pharmacol 72:477–484Google Scholar
  9. Benvenga MJ et al (2006) Attenuation of DOI-induced head twitches in mGluR2 KO mice. FASEB J 20:A246Google Scholar
  10. Berman RM et al (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354PubMedGoogle Scholar
  11. Blin J et al (1993) Loss of brain 5-HT2 receptors in Alzheimer’s disease. Brain 116:497–510PubMedGoogle Scholar
  12. Bodkin JA et al (1995) Buprenorphine treatment of refractory depression. J Clin Psychopharmacol 15:49–57PubMedGoogle Scholar
  13. Bohnen NI, Albin RL (2011) The cholinergic system and Parkinson disease. Behav Brain Res 221:564–573PubMedGoogle Scholar
  14. Burgess S et al (2001) Lithium for maintenance treatment of mood disorders. Cochrane Database Syst. Rev., (2):CD003013Google Scholar
  15. Canal CE, Morgan D (2012) Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test Anal 4:556–576PubMedPubMedCentralGoogle Scholar
  16. Carli M et al (2006) Dissociable contribution of 5-HT1AA and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. Neuropsychopharmacology 31:757–767PubMedGoogle Scholar
  17. Carlson ET, Simpson MM (1963) Opium as a tranquilizor. Am J Psychiatry 120:112–117PubMedGoogle Scholar
  18. Carpenter LL, Yasmin S, Price LH (2002) A double-blind placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry 51:183–188PubMedGoogle Scholar
  19. Chen, CPL-H et al (1998) Post-synaptic 5-HT1A and 5-HT2A receptors are increased in Parkinson’s disease neocortex. Ann NY Acad Sci 861: 288–289 Google Scholar
  20. Ciliax BJ et al (2000) Dopamine D5 receptor immunolocalization in rat and monkey brain. Synapse 37:125–145PubMedGoogle Scholar
  21. Cross AJ et al (1984) Serotonin receptor changes in dementia of the Alzheimer type. J Neurochem 43:1574–1581PubMedGoogle Scholar
  22. Cross AJ et al (1986) The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiol Aging 7:3–7PubMedGoogle Scholar
  23. Cummings J et al (2014) Pimavanserin for patients with Parkinson’s disease psychosis: a randomized, placebo-controlled phase 3 trial. Lancet 383:533–540PubMedGoogle Scholar
  24. Czyrak A et al (1993) Pharmacological effects of zotipine and other antipsychotics on the central 5-HT2 receptors. Pharmacopsychiatry 26:53–58PubMedGoogle Scholar
  25. Delille HK et al (2012) Heterocomplex formation of 5-HT(2A)-mGlu(2) and its relevance for cellular signaling cascades. Neuropharmacology 62:2183–2190Google Scholar
  26. Delille HK, Mezler M, Marek GJ (2013) The two faces of the pharmacological interaction of mGlu2 and 5-HT2A—relevance of receptor heterocomplexes and interaction through functional brain pathways. Neuropharmacology 70:296–305Google Scholar
  27. Ding YQ et al (1996) Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat. J Comp Neurol 364:290–310PubMedGoogle Scholar
  28. Doumazane E et al (2011) A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. FASEB J. 25:66–77PubMedGoogle Scholar
  29. Drevets WC, Furey ML (2010) Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry 67:432–438PubMedPubMedCentralGoogle Scholar
  30. Dunn RT, Richards JB, Seiden LS (1993) Effects of salbutamol upon performance on an operant screen for antidepressant drugs. Psychopharmacology 113:1–10PubMedGoogle Scholar
  31. Dursun SM, Handley SL (1996) Similarities in the pharmacology of spontaneous and DOI-induced head-shakes suggest 5-HT2A receptors are active under physiological conditions. Psychopharmacology 128:198–205PubMedGoogle Scholar
  32. Egashira N et al (2011) Role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice. Pharmacol Biochem Behav 99:52–58PubMedGoogle Scholar
  33. Eison AS et al (1990) Nefazodone: preclinical pharmacology of a new antidepressant. Psychopharmacol Bull 26:311–315PubMedGoogle Scholar
  34. Ellis JS et al (2014) Antidepressant treatment history as a predictor of response to scopolamine: clinical implications. J Affect Disord 162:39–42PubMedPubMedCentralGoogle Scholar
  35. Emrich HM, Voght P, Herz (1982) Possible antidepressive effects of opioids: action of buprenorphine. Ann NY Acad Sci 398:108–112PubMedGoogle Scholar
  36. Fell MJ et al (2011) N-(4-((2-trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: in vivo profiling suggests a link between behavioral and central nervous system neurochemical changes. J Pharmacol Exp Ther 336:165–177PubMedGoogle Scholar
  37. Ferreri M et al (2001) Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. Acta Psychiatr Scand 103:66–72PubMedGoogle Scholar
  38. Fitch TE, Benvenga MJ, Jesudason CD, Zink C, Vandergriff AB, Menezes MM, Schober DA, Rorick-Kehn LM, (2014) LSN2424100: a novel, potent orexin-2 receptor antagonist with selectivity over orexin-1 receptors and activity in an animal model predictive of antidepressant-like efficacy. Front Neurosci 8(Article 5): 1–11Google Scholar
  39. French Clozapine Parkinson Study Group (1999) Clozapine in drug-induced psychosis in Parkinson’s disease. Lancet 353: 2041–2042Google Scholar
  40. Fribourg M et al (2011) Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 147:1011–1023PubMedPubMedCentralGoogle Scholar
  41. Friedman E, Cooper TB, Dallob A (1983) Effects of chronic antidepressant treatment on serotonin receptor activity in mice. Eur J Pharmacol 89:69–76PubMedGoogle Scholar
  42. Furey ML, Drevets WC (2006) Antidepressant efficacy of the antimuscarinic drug scopolamine. Arch Gen Psychiatry 63:1121–1129PubMedPubMedCentralGoogle Scholar
  43. Gao W-J, Krimer LS, Goldman-Rakic PS (2001) Presynaptic regulation of reccurent excitation by D1 receptors in prefrontal circuits. Proc Natl Acad Sci U S A 98:295–300PubMedGoogle Scholar
  44. Gaynor CM, Handley SL (2001) Effects of nicotine on head-shakes and tryptophan metabolites. Psychopharmacology 153:327–333PubMedGoogle Scholar
  45. Gewirtz JC, Marek GJ (2000) Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology 23:569–576Google Scholar
  46. Gonzalez-Maeso J et al (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–99PubMedPubMedCentralGoogle Scholar
  47. Goodwin GM, Green AR, Johnson P (1984) 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behavior following antidepressant treatment to mice. Br J Pharmacol 83:235–242PubMedPubMedCentralGoogle Scholar
  48. Gouzoulis-Mayfrank E et al (2005) Psychological effects of (S)-ketamine and N, N-dimethyltryptamine: a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry 38:301–311PubMedGoogle Scholar
  49. Granon S et al (2000) Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex. J Neurosci 20:1208–1215PubMedGoogle Scholar
  50. Hacksell U et al (2014) On the discovery and development of pimavanserin: a novel drug candidate for Parkinson’s psychosis. Neurochem Res 39:2008–2017PubMedPubMedCentralGoogle Scholar
  51. Halliday G, Lees A, Stern M (2011) Milestones in Parkinson’s disease—Clinical and pathologic features. Mov Disord 26:1015–1021PubMedGoogle Scholar
  52. Handley SL, Singh L (1986) Neurotransmitters and shaking behaviour—more than a ‘gut-bath’ for the brain. Trends Pharmacol Sci 7: 324–328Google Scholar
  53. Hasselbalch SG et al (2008) Reduced 5-HT2A receptor binding in patients with mild cognitive impairment. Neurobiol Aging 29:1380–1388Google Scholar
  54. Hayslett RL, Tizabi Y (2005) Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: Implications for Tourette’s syndrome. Pharmacol Biochem Behav 81:879–886PubMedGoogle Scholar
  55. Higgins GA et al (2003) The 5-HT2A receptor antagonist M100,907 attenuates motor and ‘impulsive-type’ behaviors produced by NMDA receptor antagonism. Psychopharmacology 170:309–319PubMedGoogle Scholar
  56. Hillhouse TM, Porter JH (2014) Ketamine, but not MK-801, produces antidepressant-like effects in rats responding on a differential-reinforcement-of-low-rate operant schedule. Behav Pharmacol 25:80–91PubMedGoogle Scholar
  57. Huang Q et al (1992) Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus. Proc Natl Acad Sci U S A 89:11988–11992PubMedPubMedCentralGoogle Scholar
  58. Huot P et al (2010) Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations. Mov Disord 25:1399–1408PubMedGoogle Scholar
  59. Jakab RL, Goldman-Rakic PS (1998) 5-HT2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogens in pyramidal cell apical dendrites. Proc Natl Acad Sci USA 95:735–740PubMedPubMedCentralGoogle Scholar
  60. Karp JF et al (2014) Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry 75:e785–e793PubMedPubMedCentralGoogle Scholar
  61. Kent JM et al (2016) Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression. Prog Neuro-Psychopharmacol Biol Psychiatry 67:66–73Google Scholar
  62. Khajavi D et al (2012) Oral scopolamine augmentation in moderate to severe major depressive disorder: A randomized, double-blind, placebo-controlled study. J Clin Psychiatry 73:1428–1433PubMedGoogle Scholar
  63. Klodzinska A, et al (2002) Group II mGlu receptor agonists inhibit behavioral and electrophysiological effects of DOI in mice. Pharmacol. Biochem. Behav 73: 327–332Google Scholar
  64. Kolaj M et al (2014) Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons. Front Behav Neurosci 8:132PubMedPubMedCentralGoogle Scholar
  65. Koskinen T, Sirvio J (2001) Studies on the involvement of the dopaminergic system in the 5-HT2 agonist (DOI)-induced premature responding in a five-choice serial reaction time task. Br Res Bull 54:65–75Google Scholar
  66. Koskinen T, Haapalinna A, Sirvio J (2003) Alpha-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task. Pharmacol Toxicol 92:214–225PubMedGoogle Scholar
  67. Kosten TR, Morgan C, Kosten TA (1990) Depressive symptoms during buprenorphine treatment of opioid abusers. J Substance Abuse Treatment 7:51–54Google Scholar
  68. Lai MK et al (2005) Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer’s disease. Psychopharmacology 179:673–677PubMedGoogle Scholar
  69. Lambe EK, Aghajanian GK (2001) The role of Kv1.2-containing potassium channels in serotonin-induced glutamate release from thalamocortical terminals in rat frontal cortex. J Neurosci 21: 9955–9963PubMedGoogle Scholar
  70. Lambe EK, Aghajanian GK (2003) Hypocretin (orexin) induces calcium transients in single spines postsynaptic to identified thalamocortical boutons in prefrontal slice. Neuron 40:139–150PubMedGoogle Scholar
  71. Lambe EK, Aghajanian GK (2007) Prefrontal cortical network activity: opposite effects of psychedelic hallucinogens and D1/D5 dopamine receptor activation. Neuroscience 145:900–910PubMedPubMedCentralGoogle Scholar
  72. Lambe EK, Picciotto MR, Aghajanian GK (2003) Nicotine induces glutamate release from thalamocortical terminals in prefrontal cortex. Neuropsychopharmacology 28:216–225PubMedGoogle Scholar
  73. Lambe EK, Olausson P, Horst NK, Taylor JR, Aghajanian GK (2005) Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat. J Neurosci 25:5225–5229PubMedGoogle Scholar
  74. Lambe EK, Liu RJ, Aghajanian GK (2007) Schizophrenia, hypocretin (orexin), and the thalamocortical activating system. Schizophr Bull 33:1284–1290PubMedPubMedCentralGoogle Scholar
  75. Langlois X et al (2001) Detailed distribution of neurokinin 3 receptors in the rat, guinea pig and gerbil brain: a comparative autoradiographic study. Neuropharmacology 40:242–253PubMedGoogle Scholar
  76. Lebrand C et al (1996) Transient uptake and storage of serotonin in developing thalamic neurons. Neuron 17:991–1003Google Scholar
  77. Lecrubier Y et al (1980) A beta adrenergic stimulant (salbutamol) versus clomipramine in depression: a controlled study. Br J Psychiatry 136:354–358PubMedGoogle Scholar
  78. Li N et al (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964PubMedPubMedCentralGoogle Scholar
  79. Li N et al (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69:754–761PubMedPubMedCentralGoogle Scholar
  80. Liu RJ, Fuchikami M, Dwyer JM, Lepack AE, Duman RS, Aghajanian GK (2013) GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology 38:2268–2277PubMedPubMedCentralGoogle Scholar
  81. Lorke DE et al (2006) Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients. BMC Neurosci 7:36PubMedPubMedCentralGoogle Scholar
  82. Maes M et al (1999) Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance. J Clin Psychopharmacol 19:177–182PubMedGoogle Scholar
  83. Mansour A et al (1992) A comparison of D1 receptor binding and mRNA in rat brain using receptor autoradiographic and in situ hybridization techniques. Neuroscience 46:959–971PubMedGoogle Scholar
  84. Marder SR (1999) Limitations of dopamine-D2 antagonists and the search for novel antipsychotic strategies. Neuropsychopharmacology 21(S6):S117–S121Google Scholar
  85. Marek GJ (2003) Behavioral evidence for μ-opioid and 5-HT2A receptor interactions. Eur J Pharmacol 474:77–83PubMedGoogle Scholar
  86. Marek GJ (2009) Activation of adenosine1 (A1) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats. Neuropharmacology 56:1082–1087PubMedPubMedCentralGoogle Scholar
  87. Marek GJ (2012) Activation of adenosine1 receptors induces antidepressant-like, anti-impulsive effects on differential reinforcement of low-rate 72-s behavior in rats. J Pharmacol Exp Ther 341:564–570PubMedPubMedCentralGoogle Scholar
  88. Marek GJ, Aghajanian GK (1998a) 5-HT-induced EPSCs in neocortical layer V pyramidal cells: suppression by µ-opiate receptor activation. Neuroscience 86:485–497PubMedPubMedCentralGoogle Scholar
  89. Marek GJ, Aghajanian GK (1998b) The electrophysiology of prefrontal 5-HT systems: therapeutic implications for mood and psychosis. Biol Psychiat 44:1118–1127PubMedGoogle Scholar
  90. Marek GJ, Aghajanian GK (1999) 5-HT2A or α1-adrenoceptor activation induces excitatory postsynaptic currents in layer V pyramidal cells of the medial prefrontal cortex. Eur J Pharmacol 367:197–206PubMedGoogle Scholar
  91. Marek GJ, Seiden LS (1988) Effects of selective 5-hydroxytryptamine-2 and nonselective 5-hydroxytryptamine antagonists on the differential-reinforcement-of-low-rate 72-second schedule. J Pharmacol Exp Ther 244(2):650–658PubMedGoogle Scholar
  92. Marek GJ, Zhang C (2008) Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex. Neurosci Lett 442(3):239–243PubMedPubMedCentralGoogle Scholar
  93. Marek GJ, Li AA, Seiden LS (1989) Selective 5-hydroxytryptamine2 antagonists have antidepressant-like effects on differential-reinforcement-of-low-rate 72-second schedule. J Pharmacol Exp Ther 250(1):52–59PubMedGoogle Scholar
  94. Marek GJ et al (2000) Physiological antagonism between 5-hydroxytryptamine2A and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 292:76–87Google Scholar
  95. Marek GJ et al (2001) A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex. Neuroscience 105:379–392PubMedPubMedCentralGoogle Scholar
  96. Marek GJ et al (2003) Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology 28:402–412PubMedGoogle Scholar
  97. Marek GJ et al (2005) The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine. Neuropsychopharmacology 30:2205–2215PubMedGoogle Scholar
  98. Marek GJ, Day M, Hudzik TJ (2016) The utility of impulsive bias and altered decision making as predictors of drug efficacy and target selection: rethinking behavioral screening for antidepressant drugs. J Pharmacol Exp Ther 356:534–548PubMedGoogle Scholar
  99. Marner L et al (2011) The reduction of baseline serotonin 2A receptors in mild cognitive impairment is stable at two-year follow-up. J Alzheimers Dis 23:453–459PubMedGoogle Scholar
  100. Meltzer CC et al (1999) PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry 156:1871–1878PubMedGoogle Scholar
  101. Meltzer HY et al (2004) Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorders. Am J Psychiatry 161:975–984PubMedGoogle Scholar
  102. Meltzer HY et al (2010) Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson’s disease psychosis. Neuropsychopharmacology 35:881–892PubMedGoogle Scholar
  103. Meltzer HY et al (2012) Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: comparison with reference dose risperidone, 6 mg/day. Schizophr Res 141:144–152PubMedGoogle Scholar
  104. Miner LAH et al (2003) Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex. Neuroscience 116:107–117PubMedPubMedCentralGoogle Scholar
  105. Mitrano DA et al (2012) Alpha-1 adrenergic receptors are localized on presynaptic elements in the nucleus accumbens and regulate mesolimbic dopamine transmission. Neuropsychopharmacology 37:2161–2172PubMedPubMedCentralGoogle Scholar
  106. Moore NA et al (1992) The pharmacology of olanzapine, a novel “atypical” antipsychotic agent. J Pharmacol Exp Ther 262:545–551PubMedGoogle Scholar
  107. Moreno JL et al (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79PubMedPubMedCentralGoogle Scholar
  108. Moreno JL et al (2012) Identification of three residues essential for 5-hydroxtryptamine 2A-metabotropic glutamate 2 (5-HT2A-mGlu2) receptor heteromerizaiton and its psychoactive behavioral function. J Biol Chem 287:44301–44319PubMedPubMedCentralGoogle Scholar
  109. Muguruza C et al (2014) Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: effect of antidepressant treatment. Neuropharmacology 86:311–318PubMedGoogle Scholar
  110. Nacca A et al (1998) Brain-to-blood partition and in vivo inhibition of 5-hydroxytryptamine reuptake and quipazine-mediated behaviour of nefazodone and its main active metabolites in rodents. Br J Pharmacol 1998:1617–1623Google Scholar
  111. Narboux-Neme N et al (2008) Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhbitors (SSRIs). Neuropharmacology 55:994–1005PubMedGoogle Scholar
  112. Nelson JC, Papakostas GI (2009) Atypical antipsychotic augmentation in major depressive disorders: A meta-analysis of placebo-controlled randomized trials. Am J Psychiatry 166:980–991PubMedGoogle Scholar
  113. Neto FL et al (2000) Differential distribution of metabotropic glutamate receptor subtype mRNAs in the thalamus of the rat. Brain Res 854:93–105Google Scholar
  114. Nicholas AP, Pieribone VA, Hokfelt T (1993) Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization study. Neuroscience 56:1023–1039PubMedGoogle Scholar
  115. Nikiforuk A, Popik P, Drescher KU, van Gaalen M, Relo A-L, Mezler M, Marek G, Schoemaker H, Gross G, Bespalov A (2010) Effects of a positive allosteric modulatory of group II metabotropic glutamate receptors, LY487379, on cognitive flexibility and impulsive-like responding in rats. J Pharmacol Exp Ther 335:665–673PubMedGoogle Scholar
  116. O’Donnell JM (1990) Behavioral effects of beta adrenergic agonists and antidepressant drugs after down-regulation of beta-2 adrenergic receptors by clenbuterol. J Pharmacol Exp Ther 254(1):147–157PubMedGoogle Scholar
  117. O’Donnell JM (1993) Effects of the beta-2 adrenergic agonist zinterol on DRL behavior and locomotor activity. Psychopharmacology 113:89–94PubMedGoogle Scholar
  118. O’Donnell JM (1987) Effects of clenbuterol and prenalterol on performance during differential reinforcement of low response rate in the rat. J Pharmacol Exp Ther 241:68–75PubMedGoogle Scholar
  119. O’Donnell JM (1988) Behavioral consequences of activation of beta adrenergic receptors by clenbuterol: evidence for mediation by the central nervous system. Br Res 21(3):491–497Google Scholar
  120. O’Donnell JM, Frith S, Wilkens J (1994) Involvement of beta-1 and beta-2 adrenergic receptors in the antidepressant-like effects of centrally administered isoproterenol. J Pharmacol Exp Ther 271:246–254PubMedGoogle Scholar
  121. O’Donnell JM, Marek GJ, Seiden LS (2005) Antidepressant effects assessed using behavior maintained under a differential-reinforcement-of-low-rate (DRL) operant schedule. Neurosci Biobehav Rev 29:785–798PubMedGoogle Scholar
  122. Palucha-Poniewierg A et al (2008) Peripheral administration of group III mGlu receptor agonist ACPT-I exerts potential antipsychotic effects in rodents. Neuropharmacology 55:517–524Google Scholar
  123. Parkinson Study Group (1999) Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Eng J Med 340:757–763Google Scholar
  124. Passetti F, Dalley JW, Robbins TW (2003) Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using rodenet five-choice reaction time test. Psychopharmacology 2003:136–145Google Scholar
  125. Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological function. Science 212:827–829PubMedGoogle Scholar
  126. Perry EK et al (1984) Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer’s disease: comparisons with Parkinson’s disease. Neurosci Lett 51:353–357PubMedGoogle Scholar
  127. Petrou M, Kotagel V, Bohnen NI (2012) An update on brain imaging in Parkinson’s dementia. Imaging Med 4:201–213PubMedPubMedCentralGoogle Scholar
  128. Preskorn SH et al (2008) An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 28:631–637PubMedGoogle Scholar
  129. Rainbow TC, Parsons B, Wolfe BB (1984) Quantitative autoradiography of β1- and β2-adrenergic receptors in rat brain. Proc Natl Acad Sci USA 81:1585–1589PubMedPubMedCentralGoogle Scholar
  130. Ramanathan S, Glatt SJ (2009) Serotonergic genes in psychosis of Alzheimer dementia: meta-analysis. Am J Geriatr Psychiatry 17:839–846PubMedGoogle Scholar
  131. Rasmussen NB et al (2016) 5-HT2A receptor binding in the frontal cortex of Parkinson’s disease patients and alpha-synuclein overexpressing mice: a post-mortem study. Parkinson’s Disease 2016Google Scholar
  132. Rekling JC (2004) NK-3 receptor activation depolarizes and induces an after-depolarization in pyramidal neurons in gerbil cingulate cortex. Br Res Bull 63:85–90Google Scholar
  133. Reynolds GP et al (1984) Reduced binding of [3H]ketanserin to cortical 5-HT2 receptors in senile dementia of the Alzheimer type. Neurosci Lett 44:47–51PubMedGoogle Scholar
  134. Rigby M, O’Donnell R, Rupniak NM (2005) Species differences in tachykinin receptor distribution: further evidence that the substance P (NK1) receptor predominates in human brain. J Comp Neurol 490:335–353PubMedGoogle Scholar
  135. Rojas-Corrales, MO, Gilbert-Rahola J, Mico JA (2007) Role of atypical opiates in OCD. Experimental approach through the study of 5-HT(2A/C) receptor-mediated behavior. Psychopharmacology 190: 221–231 PubMedGoogle Scholar
  136. Rojoz Z (2012) Effect of co-treatment with mirtazapine and risperidone in animal models of the positive symptoms of schizophrrenia in mice. Pharmacol Rep 64:1567–1572Google Scholar
  137. Romano C et al (1995) Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J. Comp. Neurol. 355:455–469PubMedGoogle Scholar
  138. Rorick-Kehn LM et al (2007) Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: In vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-Amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039). J Pharmacol Exp Ther 321:308–317PubMedGoogle Scholar
  139. Rotaru DC, Lewis DA, Gonzalez-Burgos G (2007) Dopamine D1 receptor activation regulates sodium-dependent EPSP amplication in rat prefrontal cortex pyramidal neurons. J Physiol 581(3):981–1000PubMedPubMedCentralGoogle Scholar
  140. Saffroy M et al (2003) Autoradiographic distribution of tachykinin NK2 binding sites in the rat brain: comparison with NK1 and NK3 binding sites. Neuroscience 116:761–773PubMedGoogle Scholar
  141. Sanchez C, Arnt J (2000) In-vivo assessment of 5-HT2A and 5-HT2C antagonistic properties of newer antipsychotics. Behav Pharmacol 11:291–298PubMedGoogle Scholar
  142. Santana N, Mengod G, Artigas F (2012) Expression of α1-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT2A receptors. Int J Neuropsychopharmacol 16:1139–1151PubMedGoogle Scholar
  143. Santhosh L et al (2009) Regional distribution and behavioral correlates of 5-HT(2A) receptors in Alzheimer’s disease with [(18)F]deuteroaltanserin and PET. Psychiatry Res 173:212–217PubMedGoogle Scholar
  144. Schreiber R et al (1995) (1-(2,5-Dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine(5-HT)2A receptors: Modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. J Pharmacol Exp Ther 273:101–112Google Scholar
  145. Shaw E, Woolley DW (1956) Some serotoninlike activities of lysergic acid diethylamide. Science 124:121–122PubMedGoogle Scholar
  146. Shughrue PJ, Lane MV, Merchenthaler I (1996) In situ hybridization analysis of the distribution of neurokinin-3 mRNA in the rat central nervous system. J Comp Neurol 372:395–414PubMedGoogle Scholar
  147. Simon P et al (1984) Beta-Receptor Stimulation in the Treatment of Depression. In: Usdin E (ed) Frontiers in Biochemical and Pharmacological Research in Depression, Raven PRess, New York, p 293Google Scholar
  148. Simonyi A et al (2005) Expression of groups I and II metabotropic glutamate receptors in the rat brain during aging. Brain Res 1043(1–2):95–106PubMedGoogle Scholar
  149. Slawinska A et al (2013) The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents. Br J Pharmacol 169:1824–1839PubMedPubMedCentralGoogle Scholar
  150. Stutzman GE, Marek GJ, Aghajanian GK (2001) Adenosine preferentially suppresses serotonin2A receptor-enhanced excitatory postsynaptic currents in layer V neurons of the rat medial prefrontal cortex. Neuroscience 105:55–69Google Scholar
  151. Talpos JC, Wilkinson LS, Robbins TW (2006) A comparison of multiple 5-HT receptors in two tasks measuring impulsivity. J. Psychopharmacol. 20:47–58PubMedGoogle Scholar
  152. Tizabi Y et al (2001) Nicotine attenuates DOI-induced head-twitch response in mice: Implications for Tourette Syndrome. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 25:1445–1457Google Scholar
  153. Trillo L et al (2013) Ascending monoaminergic systems alterations in Alzheimer’s disease. Translating basic science into clinical care. Neurosci Biobehav Rev 37:1363–1379PubMedGoogle Scholar
  154. Vinals X et al (2015) Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannobinoid CB1 and serotonin 5-HT2A receptors. PLoS Biol 13:e1002194PubMedPubMedCentralGoogle Scholar
  155. Voleti B, Navarria A, Liu RJ, Banasr M, Li M, Terwilliger R, Sanacora G, Eid T, Aghajanian G, Duman RS (2013) Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses. Biol Psychiatry 74:742–749PubMedGoogle Scholar
  156. Vollenweider FX et al (1998) Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport 9:3897–3902Google Scholar
  157. Weisstaub NV et al (2006) Cortical 5-HT2A receptor signalling modulates anxiety-like behaviors in mice. Science 313:536–540PubMedGoogle Scholar
  158. Wettstein JG, Host M, Hitchcock JM (1999) Selectivity of action of typical and atypical anti-psychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI). Prog Neuropsychopharmacol Biol Psychiatry 23:533–544PubMedGoogle Scholar
  159. Wieronska JM et al (2012) Opposing efficacy of group III mGlu receptor activators, LSP1-2111 and AMN082, in animal models of positive symptoms of schizophrenia. Psychopharmacology 220:481–494PubMedGoogle Scholar
  160. Wieronska JM et al (2013) The reversal of cognitive, but not negative or positive symptoms of schizophrenia by the mGlu2/3 receptor agonist, LY379268, is 5-HT1A dependent. Behav Brain Res 256:298–304PubMedGoogle Scholar
  161. Willins DL, Meltzer HY (1997) Direct injection of 5-HT2Areceptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther 282:699–706PubMedGoogle Scholar
  162. Wischhof L, Koch M (2012) Pretreatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression. Psychopharmacology 219:387–400Google Scholar
  163. Wischhof, L., K.J. Hollensteiner, and M. Koch, Impulsive behavior in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu2/3 receptor agonist. Behav. Pharmacol., 2011. 22: p. 805–813PubMedGoogle Scholar
  164. Wright RA, Schoepp DD (2003) Effect of chronic exposure to mGlu2/3 receptor ligands (LY354740, LY379268 or LY341495) or antipsychotic agents clozapine or haloperidol on binding to mGlu2/3 and 5-HT2A receptors in rat prelimbic cortex. Neuroscience Meeting Planner, Society for NeuroscienceGoogle Scholar
  165. Wright RA et al (2013) CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [3H]LY459477 autoradiography. Neuropharmacology 66:89–98PubMedGoogle Scholar
  166. Zarate CA et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864PubMedGoogle Scholar
  167. Zhang C, Marek GJ (2007) Group III metabotropic glutamate receptor agonists selectively suppress excitatory synaptic currents in the rat prefrontal cortex induced by 5-hydroxytryptamine2A receptor stimulation. J Pharmacol Exp Ther 320:437–447PubMedGoogle Scholar
  168. Zhang C, Marek GJ (2008a) AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog Neuro-Psychopharmacol Biol Psychiatry 32:62–71Google Scholar
  169. Zhang C, Marek GJ (2008b) AMPA receptors involvement in 5-hydroxytryptamine2A receptor-mediated prefrontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog. Neuropsychopharmacol. & Biol. Psychiatry 32:62–71Google Scholar
  170. Zhang L, Renaud LP, Kolaj M (2009) Properties of T-Type Ca2+ channel-activated slow afterhyperpolarization in thalamic paraventricular nucleus and other thalamic midline neurons. J Neurophysiol 101:2741–2750PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Global Medical Science, CNS and PainAstellas Pharma Global DevelopmentNorthbrookUSA

Personalised recommendations