Advertisement

The Effects of Hallucinogens on Gene Expression

  • David A. Martin
  • Charles D. Nichols
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 36)

Abstract

The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.

Keywords

Psychedelics 5-HT2A IEG Gene expression 

References

  1. Abi-Saab WM, Bubser M, Roth RH, Deutch AY (1999) 5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex. Neuropsychopharmacology 20:92–96PubMedCrossRefGoogle Scholar
  2. Aghajanian GK, Marek GJ (2000) Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Res Brain Res Rev 31:302–312PubMedCrossRefGoogle Scholar
  3. Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145PubMedCrossRefGoogle Scholar
  4. Alberini CM, Ghirardi M, Metz R, Kandel ER (1994) C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia. Cell 76:1099–1114PubMedCrossRefGoogle Scholar
  5. Baker EF (1964) The use of lysergic acid diethylamide (LSD) in psychotherapy. Can Med Assoc J 91:1200–1202PubMedPubMedCentralGoogle Scholar
  6. Barclay Z, Dickson L, Robertson DN, Johnson MS, Holland PJ, Rosie R, Sun L, Fleetwood-Walker S, Lutz EM, Mitchell R (2011) 5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. Biochem J 436:651–660PubMedCrossRefGoogle Scholar
  7. Barre A, Berthoux C, De Bundel D, Valjent E, Bockaert J, Marin P, Becamel C (2016) Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning. Proc Natl Acad Sci USA 113:E1382–E1391PubMedPubMedCentralCrossRefGoogle Scholar
  8. Beique JC, Imad M, Mladenovic L, Gingrich JA, Andrade R (2007) Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc Natl Acad Sci USA 104:9870–9875PubMedPubMedCentralCrossRefGoogle Scholar
  9. Benekareddy M, Nair AR, Dias BG, Suri D, Autry AE, Monteggia LM, Vaidya VA (2013) Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor. Int J Neuropsychopharmacol 16:405–415PubMedCrossRefGoogle Scholar
  10. Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E (2007) A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol Pharmacol 72:477–484CrossRefPubMedGoogle Scholar
  11. Berg KA, Maayani S, Goldfarb J, Scaramellini C, Leff P, Clarke WP (1998) Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol Pharmacol 54:94–104PubMedCrossRefGoogle Scholar
  12. Bridi MS, Abel T (2013) The NR4A orphan nuclear receptors mediate transcription-dependent hippocampal synaptic plasticity. Neurobiol Learn Mem 105:151–158PubMedPubMedCentralCrossRefGoogle Scholar
  13. Carhart-Harris RL, Williams TM, Sessa B, Tyacke RJ, Rich AS, Feilding A, Nutt DJ (2011) The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability. J Psychopharmacol 25:1562–1567PubMedCrossRefGoogle Scholar
  14. Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS (2006) Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314:140–143PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF (2006) Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 52:445–459PubMedPubMedCentralCrossRefGoogle Scholar
  16. Cohen S, Greenberg ME (2008) Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Ann Rev Cell Dev Biol 24:183–209CrossRefGoogle Scholar
  17. de Almeida J, Mengod G (2007) Quantitative analysis of glutamatergic and GABAergic neurons expressing 5-HT(2A) receptors in human and monkey prefrontal cortex. J Neurochem 103:475–486PubMedCrossRefGoogle Scholar
  18. de Bartolomeis A, Latte G, Tomasetti C, Iasevoli F (2014) Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches. Mol Neurobiol 49:484–511PubMedCrossRefGoogle Scholar
  19. Delille HK, Mezler M, Marek GJ (2013) The two faces of the pharmacological interaction of mGlu2 and 5-HT(2)A—relevance of receptor heterocomplexes and interaction through functional brain pathways. Neuropharmacology 70:296–305PubMedCrossRefGoogle Scholar
  20. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269PubMedCrossRefGoogle Scholar
  21. Erdtmann-Vourliotis M, Mayer P, Riechert U, Hollt V (1999) Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine). Brain Res Mol Brain Res 71:313–324PubMedCrossRefGoogle Scholar
  22. Erdtmann-Vourliotis M, Mayer P, Riechert U, Hollt V (2000) Prior experience of morphine application alters the c-fos response to MDMA (‘ecstasy’) and cocaine in the rat striatum. Brain Res Mol Brain Res 77:55–64PubMedCrossRefGoogle Scholar
  23. Felder CC, Kanterman RY, Ma AL, Axelrod J (1990) Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. Proc Natl Acad Sci USA 87:2187–2191PubMedPubMedCentralCrossRefGoogle Scholar
  24. Foehring RC, van Brederode JF, Kinney GA, Spain WJ (2002) Serotonergic modulation of supragranular neurons in rat sensorimotor cortex. J Neurosci 22:8238–8250PubMedCrossRefGoogle Scholar
  25. Frankel PS, Cunningham KA (2002) The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain. Brain Res 958:251–260PubMedCrossRefGoogle Scholar
  26. Frey U, Krug M, Brodemann R, Reymann K, Matthies H (1989) Long-term potentiation induced in dendrites separated from rat’s CA1 pyramidal somata does not establish a late phase. Neurosci Lett 97:135–139PubMedCrossRefGoogle Scholar
  27. Garcia EE, Smith RL, Sanders-Bush E (2007) Role of G(q) protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. Neuropharmacology 52:1671–1677PubMedPubMedCentralCrossRefGoogle Scholar
  28. Gasser P, Kirchner K, Passie T (2014) LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. J PsychopharmacolGoogle Scholar
  29. Genoud C, Knott GW, Sakata K, Lu B, Welker E (2004) Altered synapse formation in the adult somatosensory cortex of brain-derived neurotrophic factor heterozygote mice. J Neurosci 24:2394–2400PubMedCrossRefGoogle Scholar
  30. Gerber R, Barbaz BJ, Martin LL, Neale R, Williams M, Liebman JM (1985) Antagonism of L-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist? Neurosci Lett 60:207–213PubMedCrossRefGoogle Scholar
  31. Gewirtz JC, Marek GJ (2000) Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology 23:569–576PubMedCrossRefGoogle Scholar
  32. Gewirtz JC, Chen AC, Terwilliger R, Duman RC, Marek GJ (2002) Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors. Pharmacol Biochem Behav 73:317–326PubMedCrossRefGoogle Scholar
  33. Gonzalez-Maeso J, Yuen T, Ebersole BJ, Wurmbach E, Lira A, Zhou M, Weisstaub N, Hen R, Gingrich JA, Sealfon SC (2003) Transcriptome fingerprints distinguish hallucinogenic and nonhallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex. J Neurosci 23:8836–8843PubMedCrossRefGoogle Scholar
  34. Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron 53:439–452PubMedGoogle Scholar
  35. Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez 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 452:93–97PubMedPubMedCentralCrossRefGoogle Scholar
  36. Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JL, Jones KR (2002) Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci 22:6309–6314PubMedCrossRefGoogle Scholar
  37. Gresch PJ, Strickland LV, Sanders-Bush E (2002) Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors. Neuroscience 114:707–713PubMedCrossRefGoogle Scholar
  38. Griffiths RR, Richards WA, McCann U, Jesse R (2006) Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl) 187:268–283; discussion 284–292CrossRefPubMedGoogle Scholar
  39. Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R (2011) Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 218:649–665PubMedPubMedCentralCrossRefGoogle Scholar
  40. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 30:1181–1197PubMedPubMedCentralCrossRefGoogle Scholar
  41. Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 68:71–78CrossRefPubMedGoogle Scholar
  42. Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA (2000) Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci 20:3993–4001PubMedCrossRefPubMedCentralGoogle Scholar
  43. Halberstadt AL, Geyer MA (2013) Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement. Psychopharmacology 227:727–739PubMedCrossRefGoogle Scholar
  44. Halpern JH, Pope HG Jr (2003) Hallucinogen persisting perception disorder: what do we know after 50 years? Drug Alcohol Depend 69:109–119PubMedPubMedCentralCrossRefGoogle Scholar
  45. Hinz M, Arslan SC, Scheidereit C (2012) It takes two to tango: IkappaBs, the multifunctional partners of NF-kappaB. Immunol Rev 246:59–76PubMedCrossRefGoogle Scholar
  46. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR (2014) Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 28:983–992PubMedPubMedCentralCrossRefGoogle Scholar
  47. Johnson MW, Garcia-Romeu A, Griffiths RR (2017) Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse 43:55–60PubMedCrossRefGoogle Scholar
  48. Kammermeier PJ (2008) Endogenous homer proteins regulate metabotropic glutamate receptor signaling in neurons. J Neurosci 28:8560–8567PubMedCrossRefGoogle Scholar
  49. Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294:1030–1038PubMedCrossRefGoogle Scholar
  50. Krebs TS, Johansen PO (2012) Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol 26:994–1002PubMedCrossRefGoogle Scholar
  51. Kurrasch-Orbaugh DM, Parrish JC, Watts VJ, Nichols DE (2003a) A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation: the involvement of MAP kinases. J Neurochem 86:980–991PubMedCrossRefGoogle Scholar
  52. Kurrasch-Orbaugh DM, Watts VJ, Barker EL, Nichols DE (2003b) Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. J Pharmacol Exp Ther 304:229–237PubMedCrossRefGoogle Scholar
  53. Leslie JH, Nedivi E (2011) Activity-regulated genes as mediators of neural circuit plasticity. Prog Neurobiol 94:223–237PubMedPubMedCentralCrossRefGoogle Scholar
  54. Leslie RA, Moorman JM, Coulson A, Grahame-Smith DG (1993) Serotonin 2/1 C receptor activation causes a localized expression of the immediate-early gene c-fos in rat brain: evidence for involvement of dorsal raphe nucleus projection fibres. Neuroscience 53:457–463PubMedCrossRefGoogle Scholar
  55. Li Y‚ Pehrson AL‚ Waller JA‚ Dale E‚ Sanchez C‚ Gulinello M (2015) A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)’s putative role in regulating dendritic plasticity‚ cognitive processes‚ and mood in animal models of depression. Front Neurosci 9:279Google Scholar
  56. Liu RJ, Lee FS, Li XY, Bambico F, Duman RS, Aghajanian GK (2012) Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol Psychiatry 71:996–1005PubMedCrossRefGoogle Scholar
  57. Lyons MR, West AE (2011) Mechanisms of specificity in neuronal activity-regulated gene transcription. Prog Neurobiol 94:259–295PubMedPubMedCentralCrossRefGoogle Scholar
  58. Ma YL, Tsai MC, Hsu WL, Lee EH (2006) SGK protein kinase facilitates the expression of long-term potentiation in hippocampal neurons. Learn Mem 13:114–118PubMedCrossRefGoogle Scholar
  59. Mackowiak M, Chocyk A, Fijal K, Czyrak A, Wedzony K (1999) c-Fos proteins, induced by the serotonin receptor agonist DOI, are not expressed in 5-HT2A positive cortical neurons. Brain Res Mol Brain Res 71:358–363PubMedCrossRefGoogle Scholar
  60. Mackowiak M, Czyrak A, Wedzony K (2002) Inhibition of arachidonic acid cascade attenuates the induction of c-Fos proteins by DOI, 5-HT2A/2C receptor agonist, in the rat cortex. Pol J Pharmacol 54:73–76PubMedGoogle Scholar
  61. 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 292:76–87PubMedGoogle Scholar
  62. Marek GJ, Wright RA, Gewirtz JC, Schoepp DD (2001) A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex. Neuroscience 105:379–392PubMedCrossRefGoogle Scholar
  63. Marona-Lewicka D, Nichols CD, Nichols DE (2011) An animal model of schizophrenia based on chronic LSD administration: old idea, new results. Neuropharmacology 61:503–512PubMedPubMedCentralCrossRefGoogle Scholar
  64. Martin DA, Nichols CD (2016) Psychedelics recruit multiple cellular types and produce complex transcriptional responses within the brain. EBioMedicine 11:262–277PubMedPubMedCentralCrossRefGoogle Scholar
  65. Martin DA, Marona-Lewicka D, Nichols DE, Nichols CD (2014) Chronic LSD alters gene expression profiles in the mPFC relevant to schizophrenia. Neuropharmacology 83:1–8PubMedPubMedCentralCrossRefGoogle Scholar
  66. Martin D, Xu J, Porretta C, Nichols CD (2017) Neurocytometry: flow cytometric sorting of specific neuronal populations from human and rodent brain. ACS Chem Neurosci 8:356–367PubMedCrossRefGoogle Scholar
  67. Mengod G, Pompeiano M, Martinez-Mir MI, Palacios JM (1990) Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res 524:139–143PubMedCrossRefGoogle Scholar
  68. Moorman JM, Leslie RA (1998) Paradoxical effects of lithium on serotonergic receptor function: an immunocytochemical, behavioural and autoradiographic study. Neuropharmacology 37:357–374PubMedCrossRefGoogle Scholar
  69. Moreno FA, Wiegand CB, Taitano EK, Delgado PL (2006) Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry 67:1735–1740PubMedPubMedCentralCrossRefGoogle Scholar
  70. Moreno JL, Holloway T, Albizu L, Sealfon SC, Gonzalez-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79PubMedPubMedCentralCrossRefGoogle Scholar
  71. Morris SE, Cuthbert BN (2012) Research domain criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues Clin Neurosci 14:29–37PubMedPubMedCentralGoogle Scholar
  72. Muschamp JW, Regina MJ, Hull EM, Winter JC, Rabin RA (2004) Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res 1023:134–140PubMedCrossRefGoogle Scholar
  73. Nau F Jr, Yu B, Martin D, Nichols CD (2013) Serotonin 5-HT2A receptor activation blocks TNF-alpha mediated inflammation in vivo. PLoS ONE 8:e75426PubMedPubMedCentralCrossRefGoogle Scholar
  74. Nau F Jr, Miller J, Saravia J, Ahlert T, Yu B, Happel KI, Cormier SA, Nichols CD (2014) Serotonin 5-HT2 receptor activation prevents allergic asthma in a mouse model. Am J Physiol Lung Cell Mol Physiol ajplung 00138:02013Google Scholar
  75. Nichols DE (2004) Hallucinogens. Pharmacol Ther 101:131–181CrossRefPubMedGoogle Scholar
  76. Nichols CD, Sanders-Bush E (2002) A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain. Neuropsychopharmacology 26:634–642PubMedCrossRefGoogle Scholar
  77. Nichols CD, Sanders-Bush E (2004) Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase-1, C/EBP-beta and ILAD-1, a novel gene with homology to arrestins. J Neurochem 90:576–584PubMedCrossRefGoogle Scholar
  78. Nichols CD, Garcia EE, Sanders-Bush E (2003) Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration. Brain Res Mol Brain Res 111:182–188PubMedCrossRefGoogle Scholar
  79. O’Riordan K, Gerstein H, Hullinger R, Burger C (2014) The role of Homer1c in metabotropic glutamate receptor-dependent long-term potentiation. Hippocampus 24:1–6PubMedCrossRefGoogle Scholar
  80. Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16:1137–1145PubMedCrossRefGoogle Scholar
  81. Pei Q, Lewis L, Sprakes ME, Jones EJ, Grahame-Smith DG, Zetterstrom TS (2000) Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites. Neuropharmacology 39:463–470PubMedCrossRefGoogle Scholar
  82. Pei Q, Tordera R, Sprakes M, Sharp T (2004) Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene expression in the rat cortex. Neuropharmacology 46:331–339PubMedCrossRefGoogle Scholar
  83. Puig MV, Celada P, Diaz-Mataix L, Artigas F (2003) In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents. Cereb Cortex 13:870–882PubMedCrossRefGoogle Scholar
  84. Reissig CJ, Rabin RA, Winter JC, Dlugos CA (2008) d-LSD-induced c-Fos expression occurs in a population of oligodendrocytes in rat prefrontal cortex. Eur J Pharmacol 583:40–47PubMedCrossRefGoogle Scholar
  85. Richardson CL, Tate WP, Mason SE, Lawlor PA, Dragunow M, Abraham WC (1992) Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus. Brain Res 580:147–154PubMedCrossRefGoogle Scholar
  86. Riga MS, Soria G, Tudela R, Artigas F, Celada P (2014) The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs. Int J Neuropsychopharmacol 17:1269–1282PubMedCrossRefGoogle Scholar
  87. Salles A, Romano A, Freudenthal R (2014) Synaptic NF-kappa B pathway in neuronal plasticity and memory. J Physiol Paris 108:256–262PubMedCrossRefGoogle Scholar
  88. Savage C, McCabe OL (1973) Residential psychedelic (LSD) therapy for the narcotic addict. A controlled study. Arch Gen Psychiatry 28:808–814CrossRefPubMedGoogle Scholar
  89. Schindler EA, Harvey JA, Aloyo VJ (2013) Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex. Brain Res 1491:98–108PubMedCrossRefGoogle Scholar
  90. Schmid CL, Bohn LM (2010) Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a ss-arrestin2/Src/Akt signaling complex in vivo. J Neurosci 30:13513–13524PubMedPubMedCentralCrossRefGoogle Scholar
  91. Scruggs JL, Patel S, Bubser M, Deutch AY (2000) DOI-Induced activation of the cortex: dependence on 5-HT2A heteroceptors on thalamocortical glutamatergic neurons. J Neurosci 20:8846–8852PubMedCrossRefGoogle Scholar
  92. Scruggs JL, Schmidt D, Deutch AY (2003) The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats. Neurosci Lett 346:137–140PubMedCrossRefGoogle Scholar
  93. Sheng M, Greenberg ME (1990) The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4:477–485PubMedCrossRefGoogle Scholar
  94. Steward O, Wallace CS, Lyford GL, Worley PF (1998) Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21:741–751PubMedCrossRefGoogle Scholar
  95. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R (1994) Dose-response study of N, N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry 51:98–108CrossRefPubMedGoogle Scholar
  96. Taubenfeld SM, Milekic MH, Monti B, Alberini CM (2001) The consolidation of new but not reactivated memory requires hippocampal C/EBPbeta. Nat Neurosci 4:813–818PubMedCrossRefGoogle Scholar
  97. Tilakaratne N, Friedman E (1996) Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain. Eur J Pharmacol 307:211–217PubMedCrossRefGoogle Scholar
  98. Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (2007) Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 320:1–13PubMedCrossRefGoogle Scholar
  99. 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 17:2785–2795PubMedCrossRefGoogle Scholar
  100. Veyrac A, Besnard A, Caboche J, Davis S, Laroche S (2014) The transcription factor Zif268/Egr1, brain plasticity, and memory. Prog Mol Biol Transl Sci 122:89–129PubMedCrossRefGoogle Scholar
  101. Weber ET, Andrade R (2010) Htr2a Gene and 5-HT(2A) Receptor Expression in the Cerebral Cortex Studied Using Genetically Modified Mice. Front Neurosci 4Google Scholar
  102. Wilkerson JR, Tsai NP, Maksimova MA, Wu H, Cabalo NP, Loerwald KW, Dictenberg JB, Gibson JR, Huber KM (2014) A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination. Cell Rep 7:1589–1600PubMedPubMedCentralCrossRefGoogle Scholar
  103. Wischhof L, Koch M (2012) Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression. Psychopharmacology 219:387–400PubMedCrossRefGoogle Scholar
  104. 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 327:316–323PubMedCrossRefGoogle Scholar
  105. Zhai Y, George CA, Zhai J, Nisenbaum ES, Johnson MP, Nisenbaum LK (2003) Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and excitatory responses in the cerebral cortex. Neuropsychopharmacology 28:45–52PubMedCrossRefGoogle Scholar
  106. Zhang QJ, Wang S, Liu J, Ali U, Gui ZH, Wu ZH, Hui YP, Wang Y, Chen L (2010) Unilateral lesion of the nigrostriatal pathway decreases the response of interneurons in medial prefrontal cortex to 5-HT 2A/2C receptor stimulation in the rat. Brain Res 1312:127–137PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Pharmacology and Experimental TherapeuticsLSU Health Sciences CenterNew OrleansUSA

Personalised recommendations