Skip to main content

Advertisement

SpringerLink
Log in

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Mescaline is a nonselective serotonin receptor agonist. It has relatively delayed onset of action and prolonged duration. Mescaline attenuates various behavioral parameters in rats; however, no information is available about its pharmacokinetics in rats and its relation to the behavioral changes produced by the drug.

Objectives

The present study evaluates the spontaneous locomotor activity and sensorimotor gating in relation to mescaline concentrations in the serum and the brain of rats

Materials and methods

Behavioral changes induced by mescaline [10, 20, and 100 mg/kg subcutaneously (s.c.)] were evaluated in an open-field test and testing of the prepulse inhibition of acoustic startle reaction (PPI) 15 and 60 min after drug administration. The time disposition of mescaline 20 mg/kg s.c. in rat serum and brain homogenates was analyzed by gas chromatography–mass spectrometry.

Results

Mescaline produced significant inhibitory effects on locomotion in low doses and a biphasic effect with the highest dose. In the PPI test, only when tested 60 min after drug administration, all doses of mescaline disrupted PPI. Besides the experimental protocol, we have observed that approximately 50% of animals receiving 100 mg/kg died within 12 h post-injection. The serum levels of mescaline rapidly increased within 30 min and subsequently quickly decreased; however, the brain concentrations reached a maximum 1 h after administration and remained high for an additional 60 min.

Conclusions

Mescaline had a delayed onset of the main behavioral changes in rats compared to other hallucinogens. Behavioral changes correlated with the pharmacokinetics of the drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ahn HS, Makman MH (1979) Interaction of LSD and other hallucinogens with dopamine-sensitive adenylate cyclase in primate brain: regional differences. Brain Res 162:77–88

    Article  PubMed  CAS  Google Scholar 

  • Balikova M (2005) Nonfatal and fatal DOB (2,5-dimethoxy-4-bromoamphetamine) overdose. Forensic Sci Int 153:85–91

    Article  PubMed  CAS  Google Scholar 

  • Bankson MG, Cunningham KA (2001) 3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions. J Pharmacol Exp Ther 297:846–852

    PubMed  CAS  Google Scholar 

  • Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152

    Article  PubMed  CAS  Google Scholar 

  • Baselt RC (2002) Disposition of toxic drugs and chemicals in man, 6th edn. Biomedical Publications, Foster City, California (CA)

  • Bourn WM, Keller WJ, Bonfiglio JF (1978) Psychoactivity of normacromerine in animals. Life Sci 23:1175–1184

    Article  PubMed  CAS  Google Scholar 

  • Browne RG, Harris RT, Ho BT (1974) Stimulus properties of mescaline and N-methylated derivatives: difference in peripheral and direct central administration. Psychopharmacologia 39:43–56

    Article  PubMed  CAS  Google Scholar 

  • Bubenikova V, Votava M, Horacek J, Palenicek T (2005) Relation of sex and estrous phase to deficits in prepulse inhibition of the startle response induced by ecstasy (MDMA). Behav Pharmacol 16:127–130

    Article  PubMed  CAS  Google Scholar 

  • Carder B, Sbordone R (1975) Mescaline treated rats attack immobile targets. Pharmacol Biochem Behav 3:923–925

    Article  PubMed  CAS  Google Scholar 

  • Carey RJ, DePalma G, Damianopoulos E, Muller CP, Huston JP (2004) The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior. Psychopharmacology (Berl) 177:46–54

    Article  CAS  Google Scholar 

  • Charalampous KD, Kinross-Wright J (1963) Hallucinogens. Tools for research of therapeutic agents. Tex Med 59:848–852

    PubMed  CAS  Google Scholar 

  • Charalampous KD, Walker KE, Kinross-Wright J (1966) Metabolic fate of mescaline in man. Psychopharmacologia 9:48–63

    Article  PubMed  CAS  Google Scholar 

  • Chen NH, Reith ME (1995) Monoamine interactions measured by microdialysis in the ventral tegmental area of rats treated systemically with (+/−)-8-hydroxy-2-(di-n-propylamino)tetralin. J Neurochem 64:1585–1597

    Article  PubMed  CAS  Google Scholar 

  • Cohen I, Vogel WH (1970) An assay procedure for mescaline and its determination in rat brain, liver and plasma. Experientia 26:1231–1232

    Article  PubMed  CAS  Google Scholar 

  • Davis M (1987) Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists. Psychopharmacology (Berl) 93:286–291

    Article  CAS  Google Scholar 

  • Davis WM, Bedford JA, Buelke JL, Guinn MM, Hatoum HT, Waters IW, Wilson MC, Braude MC (1978) Acute toxicity and gross behavioral effects of amphetamine, four methoxyamphetamines, and mescaline in rodents, dogs, and monkeys. Toxicol Appl Pharmacol 45:49–62

    Article  PubMed  CAS  Google Scholar 

  • Eilam D, Golani I (1989) Home base behavior of rats (Rattus norvegicus) exploring a novel environment. Behav Brain Res 34:199–211

    Article  PubMed  CAS  Google Scholar 

  • EMCDDA (2004a) Report on the risk assessment of 2C-I, 2C-T-2 and 2C-T-7 in the framework of the joint action on new synthetic drugs. European monitoring Centre for Drugs and Drug Addiction (EMCDDA), Luxembourg

  • EMCDDA (2004b) Report on the risk assessment of TMA-2 in the framework of the joint action on new synthetic drugs. European monitoring Centre for Drugs and Drug Addiction (EMCDDA), Luxembourg

  • EMCDDA Joint action on NSD (2005) Summary by substance according to the EWS Progress and Yearly Reports—2004

  • Fink H, Morgenstern R, Oelssner W (1979) Psychotomimetics potentiate locomotor hyperactivity induced by dopaminergic drugs. Pharmacol Biochem Behav 11:479–482

    Article  PubMed  CAS  Google Scholar 

  • Fiorella D, Palumbo PA, Rabin RA, Winter JC (1995) The time-dependent stimulus effects of R(−)-2,5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents. Psychopharmacology (Berl) 119:239–245

    Article  CAS  Google Scholar 

  • Foltz RL, Fentiman AF Jr, Foltz RB (1980) GC/MS assays for abused drugs in body fluids. NIDA Res Monogr 32:1–198

    PubMed  CAS  Google Scholar 

  • French Identification System for Synthetic Drugs of OFDT (SINTES) (2003) Collection and toxicological analysis in the framework of SINTES

  • Geyer MA, Petersen LR, Rose GJ, Horwitt DD, Light RK, Adams LM, Zook JA, Hawkins RL, Mandell AJ (1978) The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle. J Pharmacol Exp Ther 207:837–847

    PubMed  CAS  Google Scholar 

  • Geyer MA, Light RK, Rose GJ, Petersen LR, Horwitt DD, Adams LM, Hawkins RL (1979) A characteristic effect of hallucinogens on investigatory responding in rats. Psychopharmacology (Berl) 65:35–40

    Article  CAS  Google Scholar 

  • Geyer MA, Russo PV, Masten VL (1986) Multivariate assessment of locomotor behavior: pharmacological and behavioral analyses. Pharmacol Biochem Behav 25:277–288

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 156:117–154

    Article  CAS  Google Scholar 

  • Giroud C, Augsburger M, Rivier L, Mangin P, Sadeghipour F, Varesio E, Veuthey JL, Kamalaprija P (1998) 2C-B: a new psychoactive phenylethylamine recently discovered in Ecstasy tablets sold on the Swiss black market. J Anal Toxicol 22:345–354

    PubMed  CAS  Google Scholar 

  • Gobert A, Rivet JM, Audinot V, Newman-Tancredi A, Cistarelli L, Millan MJ (1998) Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release. Neuroscience 84:413–429

    Article  PubMed  CAS  Google Scholar 

  • Golani I, Benjamini Y, Eilam D (1993) Stopping behavior: constraints on exploration in rats (Rattus norvegicus). Behav Brain Res 53:21–33

    Article  PubMed  CAS  Google Scholar 

  • Gorelick DA, Bridger WH (1977) Facilitation and disruption by mescaline and 3,4-dimethoxyphenylethylamine of shock avoidance in rats. Psychopharmacology (Berl) 52:157–163

    Article  CAS  Google Scholar 

  • Hardman HF, Haavik CO, Seevers MH (1973) Relationship of the structure of mescaline and seven analogs to toxicity and behavior in five species of laboratory animals. Toxicol Appl Pharmacol 25:299–309

    Article  PubMed  CAS  Google Scholar 

  • Harms A, Ulmer E, Kovar KA (2003) Synthesis and 5-HT2A radioligand receptor binding assays of DOMCl and DOMOM, two novel 5-HT2A receptor ligands. Arch Pharm (Weinheim) 336:155–158

    Article  CAS  Google Scholar 

  • Harris RA, Snell D, Loh HH (1978) Effects of d-amphetamine, monomethoxyamphetamines and hallucinogens on schedule-controlled behavior. J Pharmacol Exp Ther 204:103–117

    PubMed  CAS  Google Scholar 

  • Hermle L, Funfgeld M, Oepen G, Botsch H, Borchardt D, Gouzoulis E, Fehrenbach RA, Spitzer M (1992) Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research. Biol Psychiatry 32:976–991

    Article  PubMed  CAS  Google Scholar 

  • Hirschhorn ID, Winter JC (1971) Mescaline and lysergic acid diethylamide (LSD) as discriminative stimuli. Psychopharmacologia 22:64–71

    Article  PubMed  CAS  Google Scholar 

  • Johansson C, Jackson DM, Zhang J, Svensson L (1995) Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: effects of antipsychotics and other agents in rats. Pharmacol Biochem Behav 52:649–654

    Article  PubMed  CAS  Google Scholar 

  • Kaur P, Ahlenius S (1997) Potentiation of DOI-induced forward locomotion in rats by (−)-pindolol pretreatment. J Neural Transm 104:605–614

    Article  PubMed  CAS  Google Scholar 

  • Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128

    Article  PubMed  CAS  Google Scholar 

  • Krebs-Thomson K, Geyer MA (1996) The role of 5-HT(1A) receptors in the locomotor-suppressant effects of LSD: WAY-100635 studies of 8-OH-DPAT, DOI and LSD in rats. Behav Pharmacol 7:551–559

    PubMed  CAS  Google Scholar 

  • Krebs-Thomson K, Paulus MP, Geyer MA (1998) Effects of hallucinogens on locomotor and investigatory activity and patterns: influence of 5-HT2A and 5-HT2C receptors. Neuropsychopharmacology 18:339–351

    Article  PubMed  CAS  Google Scholar 

  • Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA (2006) The roles of 5-HT(1A) and 5-HT (2) receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats. Psychopharmacology (Berl) 189:319–329

    Article  CAS  Google Scholar 

  • Laing R, Siegel JA (2003) Hallucinogens. A forensic drug handbook. Academic, London

    Google Scholar 

  • Lát J (1973) The analysis of habituation. Acta Neurobiol.Exp (Wars.) 33:771–789

    Google Scholar 

  • Lejeune F, Millan MJ (2000) Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5-HT1A receptors. Eur J Neurosci 12:3265–3275

    Article  PubMed  CAS  Google Scholar 

  • Lindner W, Wainer IW (1998) Requirements for initial assay validation and publication in J. Chromatography B. J Chromatogr B Biomed Sci Appl 707:1–2

    Article  PubMed  CAS  Google Scholar 

  • Mittman SM, Geyer MA (1991) Dissociation of multiple effects of acute LSD on exploratory behavior in rats by ritanserin and propranolol. Psychopharmacology (Berl) 105:69–76

    Article  CAS  Google Scholar 

  • Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE (1997) Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives. J Med Chem 40:2997–3008

    Article  PubMed  CAS  Google Scholar 

  • Musacchio JM, Goldstein M (1967) The metabolism of mescaline-14-C in rats. Biochem Pharmacol 16:963–970

    Article  PubMed  CAS  Google Scholar 

  • National Drug Intelligence Center (2001) Information Bulletin: 2C-B (Nexus) Reappears on the Club Drug Scene. http://www.usdoj.gov/ndic/pubs0/665/665t.htm

  • Nichols DE (2004) Hallucinogens. Pharmacol Ther 101:131–181

    Article  PubMed  CAS  Google Scholar 

  • Ouagazzal A, Grottick AJ, Moreau J, Higgins GA (2001) Effect of LSD on prepulse inhibition and spontaneous behavior in the rat. A pharmacological analysis and comparison between two rat strains. Neuropsychopharmacology 25:565–575

    Article  PubMed  CAS  Google Scholar 

  • Owen S (2005) New drug discovered in Nevada County raid. http://www.news10.net/storyfull2.aspx?storyid=14931

  • Palenicek T, Bubenikova V, Votava M, Horacek J (2005a) Účinky MDMA, LSD a psilocinu na lokomoci potkana [The effects of MDMA, LSD and Psilocin on locomotion of the rat]. Adiktologie 5:120–130

    Google Scholar 

  • Palenicek T, Votava M, Bubenikova V, Horacek J (2005b) Increased sensitivity to the acute effects of MDMA (“ecstasy”) in female rats. Physiol Behav 86:546–553

    Article  CAS  Google Scholar 

  • Palenicek T, Bubenikova V, Votava M, Horacek J (2006) Účinky selektivního antagonisty serotoninového 5-HT2C receptoru SB242084 na lokomoci potkana v animálních modelech psychóz [The effects of selective antagonist of serotonin 5-HT2C receptor SB242084 on rat’s locomotion in animal models of psychosis]. Adiktologie 10:16–19

    Google Scholar 

  • Penders J, Verstraete A (2006) Laboratory guidelines and standards in clinical and forensic toxicology. Accredit Qual Assur 11:284–290

    Article  CAS  Google Scholar 

  • Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224

    Article  PubMed  CAS  Google Scholar 

  • Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH (2000) 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry 48:229–237

    Article  PubMed  CAS  Google Scholar 

  • Sbordone RJ, Wingard JA, Elliott MK, Jervey J (1978) Mescaline produces pathological aggression in rats regardless of age or strain. Pharmacol Biochem Behav 8:543–546

    Article  PubMed  CAS  Google Scholar 

  • Sbordone RJ, Wingard JA, Gorelick DA, Elliott ML (1979) Severe aggression in rats induced by mescaline but not other hallucinogens. Psychopharmacology (Berl) 66:275–280

    Article  CAS  Google Scholar 

  • Scheline R (1978) Mammalian metabolism of plant xenobiotics. Academic, London

    Google Scholar 

  • Sethy VH, Winter JC (1973) Effect of chronic treatment with mescaline upon tissue levels of the drug. Experientia 29:571–572

    Article  PubMed  CAS  Google Scholar 

  • Silva MT, Calil HM (1975) Screening hallucinogenic drugs: systematic study of three behavioral tests. Psychopharmacologia 42:163–171

    Article  PubMed  CAS  Google Scholar 

  • Silva F, Heath RG, Rafferty T, Johnson R, Robinson W (1960) Comparative effects of the administration of Taraxein, d-LSD, mescaline, and psilocybin to human volunteers. Compr Psychiatry 1:370–376

    Article  Google Scholar 

  • Sipes TA, Geyer MA (1994) Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats. Neuropharmacology 33:441–448

    Article  PubMed  CAS  Google Scholar 

  • Sipes TA, Geyer MA (1995a) 8-OH-DPAT disruption of prepulse inhibition in rats: reversal with (+)WAY 100,135 and localization of site of action. Psychopharmacology (Berl) 117:41–48

    Article  CAS  Google Scholar 

  • Sipes TE, Geyer MA (1995b) DOI disruption of prepulse inhibition of startle in the rat is mediated by 5-HT(2A) and not by 5-HT(2C) receptors. Behav Pharmacol 6:839–842

    Article  PubMed  CAS  Google Scholar 

  • Sipes TE, Geyer MA (1997) DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum. Brain Res 761:97–104

    Article  PubMed  CAS  Google Scholar 

  • Smythies JR, Sykes EA (1964) The effect of mescaline upon the conditioned avoidance response in the rat. Psychopharmacologia 6:163–172

    Article  PubMed  CAS  Google Scholar 

  • Speck LB (1957) Toxicity and effects of increasing doses of mescaline. J Pharmacol Exp Ther 119:78–84

    PubMed  CAS  Google Scholar 

  • Spinella M (2001) The Psychopharmacology of herbal medicine. Plant drugs that alter mind, brain, and behavior. The MIT Press, Cambridge

    Google Scholar 

  • Swerdlow NR, Geyer MA, Braff DL (2001) Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl) 156:194–215

    Article  CAS  Google Scholar 

  • Sykes EA (1986) Mescaline-induced motor impairment in rats, assessed by two different methods. Life Sci 39:1051–1058

    Article  PubMed  CAS  Google Scholar 

  • Trulson ME, Crisp T, Henderson LJ (1983) Mescaline elicits behavioral effects in cats by an action at both serotonin and dopamine receptors. Eur J Pharmacol 96:151–154

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider FX, Geyer MA (2001) A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain Res Bull 56:495–507

    Article  PubMed  CAS  Google Scholar 

  • Wing LL, Tapson GS, Geyer MA (1990) 5HT-2 mediation of acute behavioral effects of hallucinogens in rats. Psychopharmacology (Berl) 100:417–425

    Article  CAS  Google Scholar 

  • Yamamoto T, Ueki S (1975) Behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rats and mice. Eur J Pharmacol 32:156–162

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by projects IGA MHCR NR8785-3, IGA MHCR NR8332-3 and MEYS CR 1M0517. We thank Craig Hampson BSc (Hons) for helpful comments and language correction.

Author information

Authors and Affiliations

  1. Prague Psychiatric Center, Ústavní 91, 181 03, Prague 8, Bohnice, Czech Republic

    Tomáš Páleníček, Věra Bubeníková-Valešová & Jiří Horáček

  2. Institute of Forensic Medicine and Toxicology, 1st Medical Faculty, Charles University in Prague, 121 08, Prague 2, Czech Republic

    Marie Balíková

Authors
  1. Tomáš Páleníček
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie Balíková
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Věra Bubeníková-Valešová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiří Horáček
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomáš Páleníček.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Páleníček, T., Balíková, M., Bubeníková-Valešová, V. et al. Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose. Psychopharmacology 196, 51–62 (2008). https://doi.org/10.1007/s00213-007-0926-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-0926-5

Keywords

Search

Navigation