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

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Abstract

Evidence suggests that stimulants such asd-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 eitherd-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 notd-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) ford-amphetamine was blocked by both DA antagonists. The ability of both D1 and D2 antagonists to attenuate the stimulus effects ofd-amphetamine and cocaine raises the possibility that a synergistic (“enabling”) interaction between D1 and D2 receptors may modulate stimulant cues.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Texas Medical Branch, 77550, Galveston, TX, USA

    P. M. Callahan & K. A. Cunningham

  2. Department of Psychology, University of South Carolina, 29208, Columbia, SC, USA

    J. B. Appel

Authors
  1. P. M. Callahan
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  2. J. B. Appel
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  3. K. A. Cunningham
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Callahan, P.M., Appel, J.B. & Cunningham, K.A. Dopamine D1 and D2 mediation of the discriminative stimulus properties ofd-amphetamine and cocaine. Psychopharmacology 103, 50–55 (1991). https://doi.org/10.1007/BF02244073

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  • DOI: https://doi.org/10.1007/BF02244073

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