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Role of Serotoninergic Neurons and 5-HT Receptors in the Action of Hallucinogens

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Serotoninergic Neurons and 5-HT Receptors in the CNS

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 129))

Abstract

Brain serotonin receptors and serotoninergic pathways have received increasing attention as targets for a wide variety of therapeutic agents. Perhaps peculiar to this realm, however, are the so-called hallucinogenic drugs, which presently lack demonstrated therapeutic utility, and still remain, as they have for at least the past 50 years, pharmacological curiosities. Research into their mechanism of action is generally poorly funded, and we know relatively little about how they affect the brain, despite their continued popularity as recreational drugs among a significant proportion of the population.

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References

  • Aghajanian GK, Foote WE, Sheard MH (1968) Lysergic acid diethylamide: sensitive neuronal units in the midbrain raphe. Science 161:706–708

    Article  PubMed  CAS  Google Scholar 

  • Aghajanian GK, Foote WE, Sheard MH (1970) Action of psychotogenic drugs on single midbrain raphe neurons. J Pharmacol Exp Ther 171:178–187

    PubMed  CAS  Google Scholar 

  • Aghajanian GK, Haigler HJ (1975) Hallucinogenic indoleamines: preferential action upon presynaptic serotonin receptors. Psychopharmacol Commun 1:619–629

    PubMed  CAS  Google Scholar 

  • Aghajanian GK, Haigler HJ, Bloom FE (1972) Lysergic acid diethylamide and serotonin: direct actions on serotonin-containing neurons. Life Sci 11:615–622

    Article  CAS  Google Scholar 

  • Andén NE, Corrodi H, Fuxe K, Hokfelt T (1968) Evidence for a central 5-hydroxytryptamine receptor stimulation by lysergic acid diethylamide. Br J Pharmacol Chemother 34:1–7

    Google Scholar 

  • Andén NE, Corrodi H, Fuxe K (1971) Hallucinogenic drugs of the indolealkylamine type and central monoamine neurons. J Pharmacol Exp Ther 179:236–249

    PubMed  Google Scholar 

  • Andén NE, Corrodi H, Fuxe K, Meek JL (1974) Hallucinogenic phenethylamines: interactions with serotonin turnover and receptors. Eur J Pharmacol 25:176–184

    Article  PubMed  Google Scholar 

  • Arnt J, Hyttel J (1989) Facilitation of 8-OH-DPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51

    Article  PubMed  CAS  Google Scholar 

  • Ashby CR Jr, Edwards E, Wang RY (1994) Electrophysiological evidence for a functional interaction between 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex: an iontophoretic study. Synapse 17:173–181

    Article  PubMed  CAS  Google Scholar 

  • Backus LI, Sharp T, Grahame-Smith DG (1990) Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. Br J Pharmacol 100:793–799

    Article  PubMed  CAS  Google Scholar 

  • Barr HL, Langs RJ, Holt RR, Goldberger L, Klein GS (1972) LSD: personality and experience. Wiley-Interscience, New York

    Google Scholar 

  • Berendsen HHG (1991) Behavioural consequences of selective activation of 5-HT receptor subtypes; possible implications for the mode of action of antidepressants. PhD thesis, University of Groningen, The Netherlands

    Google Scholar 

  • Berendsen HHG, Broekkamp CLE (1990) Behavioural evidence for functional interactions between 5-HT receptor subtypes in rats and mice. Br J Pharmacol 101:667–673

    Article  PubMed  CAS  Google Scholar 

  • Branchek T, Adham N, Macchi M, Kao H-T, Hartig PR (1990) [3H]-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H]ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor. Mol Pharmacol 38:604–609

    PubMed  CAS  Google Scholar 

  • Brandao ML, Lopez-Garcia JA, Graeff FG, Roberts MHT (1991) Electrophysiological evidence for excitatory 5-HT2 and depressant 5-HT1A receptors on neurones of the rat midbrain tectum. Brain Res 556:259–266

    Article  PubMed  CAS  Google Scholar 

  • Buckholtz NS, Zhou D, Freedman DX (1988) Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors in rat brain. Life Sci 42:2439–2445

    Article  PubMed  CAS  Google Scholar 

  • Burris KD, Breeding M, Sanders-Bush E (1991) (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist. J Pharmacol Exp Ther 258:891–896

    PubMed  CAS  Google Scholar 

  • Burt DR, Creese I, Snyder SH (1976) Binding interactions of lysergic acid diethylamide and related agents with dopaminergic receptors in brain. Mol Pharmacol 12:631–638

    PubMed  CAS  Google Scholar 

  • Cerletti A, Doepfner W (1958) Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and of ergot alkaloids. J Pharmacol Exp Ther 122:124–136

    PubMed  CAS  Google Scholar 

  • Cerletti A, Rothlin E (1955) Role of 5-hydroxytryptamine in mental disease and its antagonism to lysergic acid derivatives. Nature 176:785–786

    Article  PubMed  CAS  Google Scholar 

  • Cholden LS, Kurland A, Savage C (1955) Clinical reactions and tolerance to LSD in chronic schizophrenia. J Nerv Ment Dis 122:211–221

    Article  PubMed  CAS  Google Scholar 

  • Colpaert FC, Janssen PAJ (1983) A characterization of LSD-antagonist effects of pirenperone in the rat. Neuropharmacology 22:1001–1005

    Article  PubMed  CAS  Google Scholar 

  • Colpaert FC, Niemegeers CJE, Janssen PAJ (1982) A drug discrimination analysis of lysergic acid diethylamide (LSD): in vivo agonist and antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD-antagonist. J Pharmacol Exp Ther 221:206–214

    PubMed  CAS  Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) The dopamine receptor: differential binding of d-LSD and related agents to agonist and antagonist states. Life Sci 17:1715–1720

    Article  Google Scholar 

  • Cunningham KA, Appel JB (1987) Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD). Psychopharmacology 91:67–73

    Article  PubMed  CAS  Google Scholar 

  • Darmani NR, Martin BR, Pandey U, Glennon RA (1990) Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacol Biochem Behav 36:901–906

    Article  PubMed  CAS  Google Scholar 

  • Davis M, Sheard MH (1974) Biphasic dose-response effects of N-N-dimethyltryptamine on the rat startle reflex. Pharmacol Biochem Behav 2:827–829

    Article  PubMed  CAS  Google Scholar 

  • Deliganis AV, Pierce PA, Peroutka SJ (1991) Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors. Biochem Pharmacol 41:1739–1744

    Article  PubMed  CAS  Google Scholar 

  • DeMontigny C, Aghajanian GK (1977) Preferential action of 5-methoxytryptamine and 5-methoxydimethyltryptamine on presynaptic serotonin receptors: a comparative iontophoretic study with LSD and serotonin. Neuropharmacology 16:811–818

    Article  CAS  Google Scholar 

  • DeVivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampus membranes. J Pharmacol Exp Ther 238:248–253

    CAS  Google Scholar 

  • Dixon AK (1968) Evidence of catecholaminergic mediation in the “aberrant” behavior induced by lysergic acid diethylamide (LSD) in the rat. Experientia 15:743–747

    Article  Google Scholar 

  • Dumuis A, Sebben M, Bockaert J (1988) Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. Mol Pharmacol 33:178–186

    PubMed  CAS  Google Scholar 

  • Fiorella D, Helsley S, Lorrain DS, Rabin RA, Winter JC (1995a) The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs III: the mechanistic basis for the supersensitivity to the LSD stimulus following serotonin depletion. Psychopharmacology 121:364–372

    Article  PubMed  CAS  Google Scholar 

  • Fiorella D, Rabin RA, Winter JC (1995b) The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs I: antagonist correlation analysis. Psychopharmacology 121:347–356

    Article  PubMed  CAS  Google Scholar 

  • Fiorella D, Rabin RA, Winter JC (1995c) Role of 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs II: reassessment of LSD false positives. Psychopharmacology 121:357–363

    Article  PubMed  CAS  Google Scholar 

  • Freedman DX (1961) Effects of LSD-25 on brain serotonin. J Pharmacol Exp Ther 134:160–166

    PubMed  CAS  Google Scholar 

  • Freedman DX (1968) On the use and abuse of LSD. Arch Gen Psychiatry 18:330–347

    Article  PubMed  CAS  Google Scholar 

  • Freedman DX, Aghajanian GK, Ornitz EM, Rosner BS (1958) Patterns of tolerance to lysergic acid diethylamide and mescaline in rats. Science 127:1173–1174

    Article  PubMed  CAS  Google Scholar 

  • Freedman DX, Gottleib R, Lovell RA (1970) Psychotomimetic drugs and brain 5-hydroxytryptamine metabolism. Biochem Pharmacol 19:1181–1188

    Article  CAS  Google Scholar 

  • Fuxe K, Holmstedt B, Jonsson G (1972) Effects of 5-methoxy-N,N-dimethyltryptamine on central monoamine neurons. Eur J Pharmacol 19:25–34

    Article  PubMed  CAS  Google Scholar 

  • Gaddum JH (1953) Antagonism between lysergic acid diethylamide and 5-hydroxytryptamine. J Physiol (Lond) 121:15P

    PubMed  CAS  Google Scholar 

  • Gaddum JH, Hameed KA (1954) Drugs which antagonize 5-hydroxytryptamine. Br J Pharmacol 9:240–248

    CAS  Google Scholar 

  • Gallaher TK, Chen K, Shih J (1993) Higher affinity of psilocin for human than rat 5-HT2 receptor indicates binding site structure. Med Chem Res 3:52–66

    CAS  Google Scholar 

  • Ginzel KH, Mayer-Gross W (1956) Prevention of psychological effects of d-lysergic acid diethylamide (LSD 25) by its 2-brom derivative (BOL 148). Nature 178:210

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA (1990) Do classical hallucinogens act as 5-HT2 agonists or antagonists? Neuropsychopharmacology 3:509–517

    PubMed  CAS  Google Scholar 

  • Glennon RA (1991) Multiple populations of serotonin receptors may modulate the behavioral effects of serotoninergic agents. Life Sci 48:2493–2498

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA, Young R, Rosecrans J A (1983) Antagonism of the stimulus effects of the hallucinogen DOM and the purported serotonin agonist quipazine by 5-HT2 antagonists. Eur J Pharmacol 91:189–192

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA, Young R, Hauck AE, McKenney JD (1984a) Structure activity studies on amphetamine analogues using drug discrimination methodology. Pharmacol Biochem Behav 21:895–901

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA, Titeler M, McKenney JD (1984b) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Eur J Pharmacol 35:2505–2511

    CAS  Google Scholar 

  • Glennon RA, Titeler M, Young R (1986) Structure-activity relationships and mechanisms of action of hallucinogenic agents based on drug discrimination and radioligand binding studies. Psychopharmacol Bull 22:953–958

    PubMed  CAS  Google Scholar 

  • Gogerty JH, Dille JM (1957) Pharmacology of d-lysergic acid morpholide (LSM). J Pharmacol Exp Ther 120:340–348

    PubMed  CAS  Google Scholar 

  • Grof S (1975) Realms of the human unconscious. Observations from LSD research. Viking, New York

    Google Scholar 

  • Haigler HJ, Aghajanian GK (1975) Mescaline and LSD: direct and indirect effects on serotonin-containing neurons in brain. Eur J Pharmacol 21:53–60

    Article  Google Scholar 

  • Hamon M, Gozlan H, Mestikawy SEL, Emerit MB, Bolanol F, Schechter L (1990) The central 5-HT1A receptors: pharmacological, biochemical, functional, and regulatory properties. Ann N Y Acad Sci 600:114–131

    Article  PubMed  CAS  Google Scholar 

  • Hollister LE (1984) Effects of hallucinogens in humans. In: Jacobs BL (ed) Hallucinogens: neurochemical, behavioral, and clinical perspectives. Raven, New York, pp 19–33

    Google Scholar 

  • Hoyer D (1988) Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res 8:59–81

    PubMed  CAS  Google Scholar 

  • Huang X, Nichols DE (1993) 5-HT2 receptor-mediated potentiation of dopamine synthesis and central serotonergic deficits. Eur J Pharmacol 238:291–296

    Article  PubMed  CAS  Google Scholar 

  • Ichikawa J, Meltzer HY (1995) DOI, a 5-HT2A/2C receptor agonist, potentiates amphetamine-induced dopamine release in rat striatum. Brain Res 698:204–208

    Article  PubMed  CAS  Google Scholar 

  • Isbell H, Belleville RE, Fraser HF, Wikler A, Logan CR (1956) Studies on lysergic acid diethylamide (LSD-25). I. Effects in former morphine addicts and development of tolerance during chronic intoxication. Arch Neurol Psychiatty 76:468–478

    Google Scholar 

  • Isbell H, Miner EJ, Logan CR (1959) Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25). Psychopharmacology 1:20–28

    Article  CAS  Google Scholar 

  • Ismaiel AM, De Los Angeles J, Teitler M, Ingher S, Glennon RA (1993) Antagonism of l-(2,5-dimethoxy-4-methyl)-2-aminopropane stimulus with a newly identified 5-HT2 versus 5-HT1C-selective antagonist. J Med Chem 36:2519–2525

    Article  PubMed  CAS  Google Scholar 

  • Jaffe JH (1990) Drug addiction and drug abuse. In: Gilman AG, Rail TW, Nies AS, Taylor P (eds) Goodman and Gilman’s The pharmacological basis of therapeutics, 8th edn. McGraw-Hill, New York, pp 522–573

    Google Scholar 

  • Johnson MP, Loncharich RJ, Baez M, Nelson DL (1994) Species variations in transmembrane region V of the 5-hydroxytryptamine Type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines. Mol Pharmacol 45:277–286

    PubMed  CAS  Google Scholar 

  • Kao H-T, Adham N, Olsen MA, Weinshank RL, Branchek TA, Hartig PR (1992) Site-directed mutagenesis of a single residue changes the binding properties of the serotonin 5-HT2 receptor from a human to a rat pharmacology. FEBS Lett 307:324–328

    Article  PubMed  CAS  Google Scholar 

  • Kennett GA, Wood MD, Glen A, Grewal S, Forbes I, Gadre A, Blackburn TP (1994) In vivo properties of SB 200,646A, a novel 5-HT2C/2B receptor antagonist. Br J Pharmacol 111:797–802

    Article  PubMed  CAS  Google Scholar 

  • Leonard BE (1973) Some effects of the hallucinogenic drug 2,5-dimethoxy-4-methylamphetamine on the metabolism of biogenic amines in the rat brain. Psychopharmacologia 32:33–49

    Article  PubMed  CAS  Google Scholar 

  • Leysen JE (1985) Serotonin receptor binding sites. In: Green AR (ed) Neuropharmacology of serotonin. Oxford Press, Oxford, pp 86–87

    Google Scholar 

  • Leysen JE, Pauwels PJ (1990) 5-HT2 receptors, roles and regulation. In: Whitaker-Azmitia PM, Peroutka SJ (eds) The neuropharmacology of serotonin. Ann N Y Acad Sci 600:183–193

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) [3H]-ketanserin (R 41,468), a selective 3H-ligand for serotonin2 receptor binding sites. Mol Pharmacol 21:301–304

    PubMed  CAS  Google Scholar 

  • Leysen JE, Janssen PFM, Niemegeers CJE (1989) Rapid desensitization and down-regulation of 5-HT2 receptors by DOM treatment. Eur J Pharmacol 163:145–149

    Article  PubMed  CAS  Google Scholar 

  • Lucki I, Nobler MS, Frazer A (1984) Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther 228:1133–1139

    Google Scholar 

  • Marona-Lewicka D, Nichols DE (1995) Complex stimulus properties of LSD: a drug discrimination study with (α2-adrenoceptor agonists and antagonists. Psychopharmacology 120:384–391

    Article  PubMed  CAS  Google Scholar 

  • Martin LL, Sanders-Bush E (1982) Comparison of the pharmacological characteristics of 5-HT1 and 5-HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn Schmiedebergs Arch Pharmacol 321:165–170

    Article  PubMed  CAS  Google Scholar 

  • McClue SJ, Brazell C, Stahl SM (1989) Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor. Biol Psychiatry 26:297–302

    Article  PubMed  CAS  Google Scholar 

  • McKenna DJ, Saavedra JM (1987) Autoradiography of LSD and 2,5-dimethoxy-phenylisopropylamine psychotomimetics demonstrates regional, specific cross-displaccement in the rat brain. Eur J Pharmacol 142:313–315

    Article  PubMed  CAS  Google Scholar 

  • McKenna DJ, Nazarali AJ, Himeno A, Saavedra JM (1989) Chronic treatment with (3)-DOI, a psychotomimetic 5-HT2 agonist, downregulates 5-HT2 receptors in rat brain. Neuropsychopharmacology 2:81–87

    Article  PubMed  CAS  Google Scholar 

  • McKenna DJ, Repke DB, Peroutka SJ (1990) Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology 29:193–198

    Article  PubMed  CAS  Google Scholar 

  • Meert TF, de Haes P, Janssen PAJ (1989) Risperidone (R 64,766), a potent and complete LSD antagonist in drug discrimination by rats. Psychopharmacology 97:206–212

    Article  PubMed  CAS  Google Scholar 

  • Meert TF, De Haes PLAJ, Vermote PCM (1990) The discriminative stimulus properties of LSD: serotonergic and catecholaminergic interactions. Psychopharmacology 101:S71(271)

    Google Scholar 

  • Meibach RC, Maayani S, Green JP (1980) Characterization and radioautography of [3H]LSD binding by rat brain slices in vitro: the effect of 5-hydroxytryptamine. Eur J Pharmacol 67:371–382

    Article  PubMed  CAS  Google Scholar 

  • Meltzer HY (1991) The mechanism of action of novel antipsychotic drugs. In: Kane JM (ed) New developments in the pharmacologic treatment of schizophrenia. NIMH Public Health Service, Washington DC, pp 71–95

    Google Scholar 

  • Meltzer HY, Wiita B, Tricou BJ, Simonovic M, Fang VS, Manov G (1982) Effects of serotonin precursors and serotonin agonists on plasma hormone levels. In: Ho BT, Schoolar JC, Usdin E (eds) Serotonin in biological psychiatry. Raven Press, New York

    Google Scholar 

  • Nanry KP, Tilson HA (1989) The role of 5-HT1A receptors in the modulation of the acoustic startle reflex in rats. Psychopharmacology (Berlin) 97:507–513

    Article  PubMed  CAS  Google Scholar 

  • Nelson DL, Lucaites VL, Audia JE, Nissen JS, Wainscott DB (1993) Species differences in the pharmacology of the 5-hydroxytrypamine2 receptor: structurally specific differentiation by ergolines and tryptamines. J Pharmacol Exp Ther 265:1271–1279

    Google Scholar 

  • Nichols DE (1994) Medicinal chemistry and structure-activity relationships. In: Cho AK, Segal DS (eds) Amphetamine and its analogs. Academic, New York, pp 3–41

    Google Scholar 

  • Nichols DE, Oberlender R, McKenna DJ (1991) Stereochemical aspects of hallucinogenesis. In: Watson RR (ed) Biochemistry and physiology of substance abuse, vol III. CRC, Boca Raton, FL, pp 1–39

    Google Scholar 

  • Nichols DE, Frescas S, Marona-Lewicka D, Huang X, Roth BL, Gudelsky GA, Nash JF (1994) 1-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5-HT2A/2C agonist. J Med Chem 37:4346–4351

    Article  PubMed  CAS  Google Scholar 

  • Nielsen EB (1985) Discriminative stimulus properties of lysergic acid diethylamide in the monkey. J Pharmacol Exp Ther 234:244–249

    PubMed  CAS  Google Scholar 

  • Norman AB, Nash DR, Sanberg PR (1989) [3H]Lysergic acid diethylamide (LSD): differential agonist and antagonist binding properties at 5-HT receptor subtypes in rat brain. Neurochem Int 14:497–504

    Article  PubMed  CAS  Google Scholar 

  • Pahnke (1963) Drugs and mysticism. An analysis of the relationship between psychedelic drugs and the mystical consciousness. PhD thesis, Harvard University

    Google Scholar 

  • Pierce PA, Peroutka SJ (1989) Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex. Psychopharmacology 97:118–122

    Article  PubMed  CAS  Google Scholar 

  • Pierce PA, Peroutka SJ (1990) Antagonist properties of d-LSD at 5-hydroxytryptamine2 receptors. Neuropsychopharmacology 3:503–508

    PubMed  CAS  Google Scholar 

  • Pompeiano M, Palacios JM, Mengod G (1994) Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Mol Brain Res 23:163–178

    Article  PubMed  CAS  Google Scholar 

  • Randic M, Padjen A (1971) Effect of N,N-dimethyltryptamine and d-lysergic acid diethylamide on the release of 5-hydroxyindoles in rat forebrain. Nature 230:532–533

    Article  PubMed  CAS  Google Scholar 

  • Resnick O, Krus DM, Raskin M (1965) Accentuation of the psychological effects of LSD-25 in normal subjects treated with reserpine. Life Sci 4:1433–1437

    Article  PubMed  CAS  Google Scholar 

  • Rogawski MA, Aghajanian GK (1979) Response of central monoaminergic neurons to lisuride: comparison with LSD. Life Sci 24:1289–1298

    Article  PubMed  CAS  Google Scholar 

  • Rosecrans JA, Lovell RA, Freedman DX (1967) Effects of lysergic acid diethylamide on the metabolism of brain 5-hydroxytryptamine. Biochem Pharmacol 16:2011–2021

    Article  PubMed  CAS  Google Scholar 

  • Sadzot B, Baraban JM, Glennon RA, Lyon RA, Leonhardt S, Jan C-R, Titeler M (1989) Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis. Psychopharmacology 98:495–499

    Article  PubMed  CAS  Google Scholar 

  • Sanders-Bush E (1994) Neurochemical evidence that hallucinogenic drugs are 5-HT1C receptor agonists: what next? In: Lin GC, Glennon RA (eds) Hallucinogens: an update. US-DHHS, Rockville, MD, pp 203–213 (NIDA research monograph series, 146)

    Google Scholar 

  • Sanders-Bush E, Breeding M (1991) Choroid plexus epithelial cells in primary culture: a model of 5-HT1C receptor activation by hallucinogenic drugs. Psychopharmacology 105:340–346

    Article  PubMed  CAS  Google Scholar 

  • Sanders-Bush E, Burris KD, Knoth K (1988) Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. J Pharmacol Exp Ther 246:924–928

    PubMed  CAS  Google Scholar 

  • Schmidt CJ, Fadayel GM, Sullivan CK, Taylor VL (1992) 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 199,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine. Eur J Pharmacol 223:65–74

    Article  PubMed  CAS  Google Scholar 

  • Schreiber R, Brocco M, Millan MJ (1994) Blockade of the discriminative stimulus effects of DOI by MDL 100,907 and the ‘atypical’ antipsychotics, clozapine and risperidone. Eur J Pharmacol 264:99–102

    Article  PubMed  CAS  Google Scholar 

  • Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (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 273:101–112

    PubMed  CAS  Google Scholar 

  • Shulgin AT, Shulgin A (1991) PIHKAL. A chemical love story. Transform, Berkeley, CA

    Google Scholar 

  • Sotelo C, Cholley B, El Mestikawy S, Gozlan H, Hamon M (1990) Direct immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci 2:1144–1154

    Article  PubMed  Google Scholar 

  • Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9

    Article  PubMed  CAS  Google Scholar 

  • Sprouse JS, Aghajanian GK (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology 27:707–715

    Article  PubMed  CAS  Google Scholar 

  • Teitler M, Leonhardt S, Weisberg EL, Hoffman BJ (1990) 4-[125I]Iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: evidence for multiple states and not multiple 5HT2 receptor subtypes. Mol Pharmacol 38:594–598

    PubMed  CAS  Google Scholar 

  • Titeler M, Lyon RA, Glennon RA (1988) Radioligand binding evidence implicates the brain 5-HT2 receptor as site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology 94:213–216

    Article  PubMed  CAS  Google Scholar 

  • Tricklebank MD, Forler C, Middlemiss DN, Fozard JR (1985) Subtypes of the 5-HT receptor mediating the behavioral responses to 5-methoxy-N,N-dimethyltryptamine in the rat. Eur J Pharmacol 117:15–24

    Article  PubMed  CAS  Google Scholar 

  • Trulson ME, Heym J, Jacobs BL (1981) Dissociations between the effects of hallucinogenic drugs on behavior and raphe unit activity in freely moving cats. Brain Res 215:275–293

    Article  PubMed  CAS  Google Scholar 

  • Twarog BM, Page I (1953) Serotonin content of some mammalian tissues and urine and a method for its determination. Am J Physiol 175:157–161

    PubMed  CAS  Google Scholar 

  • Udenfriend S, Weissbach H, Clark CT (1954) The estimation of 5-hydroxytryptamine (serotonin) in biological tissues. J Biol Chem 215:337–344

    Google Scholar 

  • U’Prichard DC, Greenberg DA, Snyder SH (1977) Binding characteristics of radiolabeled agonist and antagonists at central nervous system alpha noradrenergic receptors. Mol Pharmacol 13:454–473

    PubMed  Google Scholar 

  • Votava Z, Podvolava I, Semonsky M (1958) Studies on the pharmacology of d-lysergic acid cycloalkylamides. Arch Int Pharmacodyn Ther 115:114–130

    PubMed  CAS  Google Scholar 

  • Walker EA, Yamamoto T, Hollingsworth PJ, Smith DB, Woods JH (1991) Discriminative stimulus effects of quipazine and 1-5-hydroxytryptophan in relation to serotonin binding sites in pigeons. J Pharmacol Exp Ther 259:772–782

    PubMed  CAS  Google Scholar 

  • Wasson RG, Hofmann A, Ruck AP (1977) The road to eleusis. Harcourt Brace Jovanovich, New York, pp 17–18

    Google Scholar 

  • Watts VJ, Lawler CP, Fox DR, Neve KA, Nichols DE, Mailman RB (1995) LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors. Psychopharmacology 118:401–409

    Article  PubMed  CAS  Google Scholar 

  • Williams JT, Colmers WF, Pan ZZ (1988) Voltage and ligand activated inwardly rectifying currents in rat dorsal raphe neurons in vitro. J Neurosci 8:3499–3506

    PubMed  CAS  Google Scholar 

  • Winter JC (1994) The stimulus effects of serotonergic hallucinogens in animals. In: Lin GC, Glennon RA (eds) Hallucinogens: an update. US-DHHS, Rockville, MD, pp 157–182 (NIDA research monograph series 146)

    Google Scholar 

  • Winter JC, Rabin RA (1988) Interactions between serotonergic agonist and antagonists in rats trained with LSD as a discriminative stimulus. Pharmacol Biochem Behav 30:617–624

    Article  PubMed  CAS  Google Scholar 

  • Woolley DW, Shaw E (1954) A biochemical and pharmacological suggestion about certain mental disorders. Proc Natl Acad Sci USA 40:228–231

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T, Walker EA, Woods JH (1991) Agonist and antagonist properties of serotonergic compounds in pigeons trained to discriminate either quipazine or 1-5-hydroxytryptophan. J Pharmacol Exp Ther 258:999–1007

    PubMed  CAS  Google Scholar 

  • Yocca FD, Wright RN, Margraf RR, Eison AS (1990) 8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shakes response in rats. Pharmacol Biochem Behav 35:251–254

    Article  PubMed  CAS  Google Scholar 

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Nichols, D.E. (2000). Role of Serotoninergic Neurons and 5-HT Receptors in the Action of Hallucinogens. In: Baumgarten, H.G., Göthert, M. (eds) Serotoninergic Neurons and 5-HT Receptors in the CNS. Handbook of Experimental Pharmacology, vol 129. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60921-3_21

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