, Volume 120, Issue 3, pp 303–310 | Cite as

The discriminative stimulus effects of methamphetamine in pigeons

  • J. E. Sasaki
  • T. A. Tatham
  • J. E. Barrett
Original Investigation


This experiment was designed to elucidate the neurotransmitter systems that mediate the discriminative stimulus effects of methamphetamine. Four pigeons were trained to peck one key following saline injections and a second key following methamphetamine injections (1.0 or 1.7 mg/kg, IM). Substitution tests revealed drug-appropriate responding following administration of the psychomotor stimulants methamphetamine, amphetamine and cocaine, the dopamine (DA) reuptake inhibitor bupropion, norepinephrine (NE) reuptake inhibitors imipramine and tomoxetine, and the serotonin (5-HT) releaser fenfluramine. Salinekey responding occurred following administration of the D1 agonist SKF-38393, the D1 antagonist SCH-23390, the α2 receptor agonist clonidine, the α1 antagonist prazosin, a nonselective β-antagonist propranolol and the selective 5-HT reuptake inhibitor fluoxetine. The D2/D3 agonist quinpirole produced drug-appropriate responding in two pigeons and partial substitution in the remaining two pigeons. The 5HT1A agonist 8-OH-DPAT produced drug-appropriate responding at higher doses (0.3–1.0 mg/kg), whereas much lower doses (0.003–0.1 mg/kg) antagonized the methamphetamine stimulus. The stimulus effects of methamphetamine were attenuated by pretreatment with prazosin, SCH-23390 and eticlopride, whereas pretreatment with propranolol and the 5-HT3 antagonist, MDL 72222, failed reliably to attenuate drug key responding. These results suggest that NE and DA reuptake inhibition and 5-HT release mediate the discriminative stimulus effects of methamphetamine as do the 5-HT1A and DA D1 and D2 receptors.

Key words

Methamphetamine Drug discrimination Key pecking Pigeons Dopamine Norepinephrine Serotonin 


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  1. Ando K, Yanagita T (1992) Effects of an antitussive mixture and its constituents in rats discriminating methamphetamine from saline. Pharmacol Biochem Behav 41:783–788PubMedGoogle Scholar
  2. Bilsky EJ, Reid LD (1991) MDL 72222, a serotonin 5-HT3 receptor antagonist, blocks MDMA's ability to establish a conditioned place preference. Pharmacol Biochem Behav 39:509–512CrossRefPubMedGoogle Scholar
  3. Callahan PM, Cunningham KA (1993) Discriminative stimulus properties of cocaine in relation to dopamine D2 receptor function in rats. J Pharmacol Exp Ther 266:585–592PubMedGoogle Scholar
  4. Eilam D, Szechtman H (1989) Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur J Pharmacol 161:151–157CrossRefPubMedGoogle Scholar
  5. Glennon RA, Young R (1984) Further investigation of the discriminative stimulus properties of MDA. Pharmacol Biochem Behav 20:501–505CrossRefPubMedGoogle Scholar
  6. Grant KA, Barrett JE (1991) Blockade of the discriminative stimulus effects of ethanol with 5-HT3 receptor antagonists. Psychopharmacology 104:451–456CrossRefPubMedGoogle Scholar
  7. Helschober B, Miller MA (1991) Methamphetamine abuse in California. National Institute on Drug Abuse Research Monograph Series 115:60–71PubMedGoogle Scholar
  8. Imperato A, Angelucci L (1989) 5-HT3 receptors control dopamine release in the nucleus accumbens of freely moving rats. Neurosci Lett 101:214–217CrossRefPubMedGoogle Scholar
  9. Järbe TUC (1982) Discriminative stimulus properties ofd-amphetamine in pigeons. Pharmacol Biochem Behav 17:671–675PubMedGoogle Scholar
  10. Järbe TUC, Kroon ER (1980) Discriminative properties ofd-amphetamine in gerbils: tests for drug generalization and antagonism. Gen Pharmacol 11:153–156Google Scholar
  11. Johanson CE, Barrett JE (1993) The discriminative stimulus effects of cocaine in pigeons. J Pharmacol Exp Ther 267:1–8PubMedGoogle Scholar
  12. Kleven MS, Seiden LS (1992) Methamphetamine-induced neurotoxicity: structure and activity relationships. Ann NY Acad Sci 654:292–301PubMedGoogle Scholar
  13. Mashurano M, Waddington JL (1986) Stereotyped behavior in response to the selective D-2 dopamine receptor agonist RU24213 is enhanced by pretreatment with the selective D-1 agonist SK&F 38393. Neuropharmacology 25:947–949CrossRefPubMedGoogle Scholar
  14. Miller MA (1991) Trends and patterns of methamphetamine smoking in Hawaii. National Institute on Drug Abuse Research Monograph Series 115:72–83PubMedGoogle Scholar
  15. Oberlender R, Nichols DE (1988) Drug discrimination studies with MDMA and amphetamine. Psychopharmacology 95:71–76CrossRefPubMedGoogle Scholar
  16. Paris JM, Cunningham KA (1991) Serotonin 5-HT3 antagonists do not alter the discriminative stimulus properties of cocaine. Psychopharmacology 104:475–478CrossRefPubMedGoogle Scholar
  17. Peltier R, Schenk S (1991) GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats. Pharmacol Biochem Behav 39:133–136CrossRefPubMedGoogle Scholar
  18. Pradhan SN, Maickel RP, Dutta SN (eds) (1986) Pharmacology in medicine: principles and practice. SP Press International, Bethesda, Md., p 345Google Scholar
  19. Schechter MD, Glennon RA (1985) Cathinone, cocaine and methamphetamine: similarity of behavioral effects. Pharmacol Biochem Behav 22:913–916PubMedGoogle Scholar
  20. Schechter MD, Rosecrans JA (1973)d-Amphetamine as a discriminative cue: drugs with similar stimulus properties. Eur J Pharmacol 21:212–216CrossRefPubMedGoogle Scholar
  21. Seiden LS, Kleven MS (1991) Methamphetamine and related drugs: toxicity and resulting behavioral changes in response to pharmacological probes. NIDA Res Monogr 94:146–161Google Scholar
  22. Sokoloff P, Giros B, Martres M-P, Bourthenet M-L, Schwartz J-C (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347:146–151PubMedGoogle Scholar
  23. Tatham TA, Zurn KR (1989) The MED-PC experimental apparatus programming system. Behav Res Methods Instr Comput 21:294–302Google Scholar
  24. Wood DM, Lal H, Emmett-Oglesby M (1984) Acquisition and recovery of tolerance to the discriminative stimulus properties of cocaine. Neuropharmacology 23:1419–1423CrossRefPubMedGoogle Scholar
  25. Young R, Glennon RA (1986) Discriminative stimulus properties of amphetamine and structurally related phenylalkylamines. Med Res Rev 6:99–130PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • J. E. Sasaki
    • 1
  • T. A. Tatham
    • 1
  • J. E. Barrett
    • 2
  1. 1.Behavioral Pharmacology Laboratory, Department of Psychiatry, Uniformed ServicesUniversity of the Health SciencesBethesdaUSA
  2. 2.Lederle LaboratoriesCentral Nervous System ResearchPearl RiverUSA

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