Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine

P. M. Callahan, J. B. Appel, Kathryn Cunningham

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Evidence suggests that stimulants such as d-amphetamine and cocaine act presynaptically by increasing the amount of dopamine (DA) available to stimulate postsynaptic DA receptors. Since two subpopulations of DA receptors (D1 and D2) exist, we investigated the role of both of these receptor subtypes in mediating the internal "state" produced by these stimulants. Two groups of rats (N=8/group) were trained to discriminate intraperitoneal (IP) injections of either d-amphetamine (1 mg/kg) or cocaine (10 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination task. After stable performance was established (i.e., more than 85% correct under each training condition), substitution and combination tests were conducted with selective D1 and D2 agonists and antagonists. The D2 agonist quinpirole (0.0313-0.125 mg/kg) mimicked both stimulant cues while the D1 agoinst SKF 38393 (5-20 mg/kg) substituted partially for cocaine but not d-amphetamine. Combination tests with DA antagonists indicated that both the D1 antagonist SCH 23390 (0.0063-0.25 mg/kg) and the D2 antagonist haloperidol (0.125-0.5 mg/kg) attenuated the effects of both stimulants; in addition, the substitution of cocaine (20 mg/kg) for d-amphetamine was blocked by both DA antagonists. The ability of both D1 and D2 antagonists to attenuate the stimulus effects of d-amphetamine and cocaine raises the possibility that a synergistic ("enabling") interaction between D1 and D2 receptors may modulate stimulant cues.

Original languageEnglish (US)
Pages (from-to)50-55
Number of pages6
JournalPsychopharmacology
Volume103
Issue number1
DOIs
StatePublished - Jan 1991

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Dextroamphetamine
Cocaine
Dopamine
Dopamine Antagonists
Cues
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Quinpirole
Dopamine D1 Receptors
Aptitude
Dopamine D2 Receptors
Dopamine Receptors
Haloperidol
Intraperitoneal Injections
Water
Pharmaceutical Preparations

Keywords

  • Behavior
  • Cocaine
  • d-Amphetamine
  • Drug discrimination
  • Rat

ASJC Scopus subject areas

  • Pharmacology

Cite this

Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. / Callahan, P. M.; Appel, J. B.; Cunningham, Kathryn.

In: Psychopharmacology, Vol. 103, No. 1, 01.1991, p. 50-55.

Research output: Contribution to journalArticle

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