Abstract
The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D2 against LY-171555 (0.05–0.25 mg/kg); but not to the D1 agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D1 antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D2 antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D1 or D2 receptor activation; for example, the stimulus properties of this substance might involve both D1 and D2 receptor activation.
Similar content being viewed by others
References
Appel JB, Weathersby RT, Cunningham KA, Callahan PM, Barrett RL (1988) Stimulus properties of dopaminergic drugs: comparisons involving selective agonists and antagonists. In: Colpaert FC, Balster RL (eds) Transduction mechanisms of drug stimuli. Springer, Berlin Heidelberg New York Tokyo, pp 44–56
Broadbent J, Appel JB (1989) The behavioral pharmacology of stimulants and hallucinogens: drug discrimination and self-administration procedures. Pharmacol Ther (in press)
Carlsson A, Kehr W, Lindquist T, Magnusson T, Attack CV (1972) Regulation of monoamine metabolism in the central nervous system. Pharmacol Rev 24:371–384
Colpacrt FC, Niemegeers CJE, Janssen PAJ (1978) Discriminative stimulus properties of cocaine andd-amphetamine and antagonism by haloperidol: a comparative study. Neuropharmacology 17:937–942
Cunningham KA, Appel JB (1987) Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD). Psychopharmacology 91:67–73
Fischman MW, Schuster CR (1982) Cocaine self-administration in humans. Fed Proc 41:241–246
Goudie A, Reid D (1988) Qualitative discrimination between cocaine and amphetamine in rats. Eur J Pharmacol 151:471–474
Grigoriadis D, Seeman P (1984) The dopamine/neuroleptic receptor. Can J Neurol Sci 11:108–113
Hollander M, Wolfe D (1973) Nonparametric statistical methods. Wiley, New York, p 138
Hyttel J (1983) Sch-23390-the first selective dopamine D1 antagonist. Eur J Pharmacol 91:153–154
Jarbe TUC (1978) Cocaine as a discriminative cue in rats: interactions with neuroleptics and other drugs. Psychopharmacology 59:183–187
Jarbe TUC (1984) Discriminative stimulus properties of cocaine: effects of apomorphine, haloperidol, procaine and other drugs. Neuropharmacology 23:899–907
Jarbe TUC, Kroon ER (1980) Discriminative properties ofd-amphetamine in gerbils: tests for drug generalization and antagonism. Gen Pharmacol 11:153–156
Kebabian J, Calne D (1979) Multiple receptors of dopamine. Nature 227:93–96
Kleven MS, Anthony EW, Goldberg L, Woolverton WL (1988) Blockade of the discriminative stimulus effects of cocaine in rhesus monkeys with the D1 dopamine antagonist SCH 23390. Psychopharmacology 95:427–429
Lauduron P, Janssen PAJ, Leysen JE (1978) Spiperone: a ligand of choice for neuroleptic receptors. Biochem Pharmacol 27:317–321
Molloy A, Waddington J (1984) Dopaminergic behavior stereospecifically promoted by the D1 agonist R-SK & F-38393 and selectively blocked by the D1 antagonist Sch-23390. Psychopharmacology 82:409–410
Nielsen EB, Jepsen SA (1985) Antagonism of the amphetamine cue by both classical and atypical antipsychotic drugs. Eur J Pharmacol 11:167–178
Overton DA, Hayes MW (1980) Concurrent drug discrimination training with drugs as a method for controlling specificity. Fed Proc 39:402
Stoof J, Kebabian J (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 35:2281–2296
Tsuruta K, Frey EA, Grewe CW, Cote TE, Eskay RL, Kebabian JW (1981) Evidence that LY-141865 specifically stimulates the D2 dopamine receptor. Nature 292:463–465
Waddington JL (1986) Behavioral correlates of the action of selective D-1 dopamine receptor antagonists. Impact of SCH 23390 and SKF 83566, and functionally interactive D-1:D-2 receptor systems. Biochem Pharmacol 35:3661–3667
Walters JR, Bergstrom DA, Carlson JH, Chase TN, Braun AR (1987) D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects. Science 236:719–722
Weathersby RT, Appel JB (1986) Dopamine D2 receptor mediation of the discriminative stimulus properties of LY 171555 (quinpirole). Eur J Pharmacol 132:87–91
Wood DM, Emmett-Oglesby MW (1986) Characteristics of tolerance, recovery from tolerance and cross-tolerance for cocaine used as a discriminative stimulus. J Pharmacol Exp Ther 237:120–125
Wood DM, Lal H, Emmett-Oglesby MW (1984) Acquisition and recovery of tolerance to the discriminative stimulus properties of cocaine. Neuropharmacology 23:1419–1423
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barrett, R.L., Appel, J.B. Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine. Psychopharmacology 99, 13–16 (1989). https://doi.org/10.1007/BF00634445
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00634445