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BEHAVIORAL PHARMACOLOGY

Drug and Reinforcement History as Determinants of the Response-Maintaining Effects of Quinpirole in the Rat

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

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.

Address correspondence to: Dr. James H. Woods, Department of Pharmacology, 1301 MSRB III, University of Michigan Medical School, Ann Arbor, MI 48109-0632. E-mail: jhwoods{at}umich.edu