Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine.
Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N = 8) or 10 mg/kg (N = 8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5-20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5-40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25-5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2-16 mg/kg) produced primarily saline-appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose-response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue.
Callahan
P M
PM
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Piercey
M F
MF
Cunningham
K A
KA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018492:Dopamine Antagonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; C045971:UH 232; D003042:Cocaine