Effects of drugs on food- and cocaine-maintained responding, III: Dopaminergic antagonists.
The effects of three dopamine (DA) antagonists (SCH23390, pimozide, and chlorpromazine), with various degrees of selectivity for D1 and D2 receptors, and an agonist (the cocaine analog, CFT) were studied on responding maintained under a multiple fixed-ratio (FR) 30 food, FR30 cocaine (1-100 micrograms/kg per injection) delivery, with an interposed 10-min time-out (TO), schedule in rhesus monkeys. The effects of each drug depended upon the unit dose of cocaine. With an intermediate (10 micrograms/kg per injection) unit dose of cocaine, each antagonist decreased rates of responding maintained by either event in a dose-related manner. At higher (56-100 micrograms/kg per injection) unit doses of cocaine, antagonists generally increased and then decreased both food- and cocaine-maintained responding in a dose-related manner. These increases appeared to result from the blockade of non-specific rate-decreasing effects of self-administered cocaine, questioning their relevance to the reinforcing effects of cocaine. The results failed to support a role for pharmacological selectivity in this rate-decreasing effect of cocaine, as both D1 and D2 antagonists were able to reverse the effect. In contrast, CFT decreased cocaine-maintained responding at doses less than those that decreased food-maintained responding, and failed to shift the cocaine dose-effect function to the left. These results, together with previous work, suggest that agonists can selectively decrease drug-seeking behavior.
Glowa
J R
JR
Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892-5550, USA.
Wojnicki
F H
FH
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005502:Food; D008253:Macaca mulatta; D008297:Male; D009294:Narcotics; D010868:Pimozide / Q000494:pharmacology; D012646:Self Administration
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D010868:Pimozide; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D002746:Chlorpromazine