Drug and reinforcement history as determinants of the response-maintaining effects of quinpirole in the rat.
The present study examined the effect of drug and reinforcement history on quinpirole-maintained responding in rats. Quinpirole (0.01, 0.032, or 0.1 mg/kg per injection) was assessed as a reinforcer in experimentally naive rats, as well as in rats trained to self-administer cocaine, remifentanil, ketamine, or food under a fixed ratio 1 schedule of reinforcement. Quinpirole failed to maintain responding in experimentally naive rats, or in ketamine- or food-trained rats. However, robust responding was maintained in rats with a history of cocaine reinforcement, and modest levels of responding were observed in rats with a history of responding for remifentanil. In a second set of studies, the effects of protracted drug histories on quinpirole-maintained responding in food-trained rats were assessed. Rats were maintained with food reinforcement, and different groups of rats were then allowed to respond for saline, quinpirole, and response-contingent cocaine or were administered noncontingent cocaine; all rats were subsequently allowed to respond for quinpirole. Only rats that previously responded for cocaine showed quinpirole-maintained responding; all other conditions failed to establish quinpirole-maintained responding. Although the high levels of quinpirole-maintained responding observed when quinpirole was substituted for cocaine are suggestive of positive reinforcing effects, these response-maintaining effects were highly dependent upon both drug and reinforcement history, suggesting that quinpirole may only function as a reinforcer under very specific conditions. The behavioral effects of quinpirole under these situations represent a novel constellation of actions relative to other drug reinforcers, and they suggest that the direct effects of self-administered quinpirole may be important in establishing the response-maintaining effects.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632, USA.
Gregory T
GT
Collins
James H
JH
Woods
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D019257:Quinpirole / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists; D012054:Reinforcement, Psychology; D012646:Self Administration
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; D003042:Cocaine