A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys.

@article{citeulike:3322437, abstract = {RATIONALE: Drug discrimination (DD) and drug self-administration (SA) are frequently used preclinical assays. All preclinical studies with cocaine have examined the discriminative stimulus (S(D)) and reinforcing (S(R)) effects in separate groups of subjects. OBJECTIVE: The objective of the study is to train drug-na\"{i}ve rhesus macaques to discriminate self-administered cocaine from saline and to assess S(D) and S(R) effects using a within-subjects design. MATERIALS AND METHODS: Adult male rhesus monkeys (n = 4) were trained to self-administer cocaine (0.1 mg/kg per injection) under a progressive-ratio (PR) reinforcement schedule. Next, they were trained to discriminate self-administered cocaine (0.45 or 0.56 mg/kg) or saline under a fixed-ratio (FR) 50 schedule of food presentation. The final schedule combined DD and SA into a multiple [chained FR 50 SA (cocaine or saline), food-reinforced DD] and PR SA schedule. RESULTS: Each subject acquired SA under a PR schedule with significant differences in breakpoint between saline and cocaine evident by session 5. Self-administered cocaine was established as an S(D), such that 80\% of responding before delivery of the first reinforcer and 90\% of all responding occurred on the injection-appropriate lever. In all monkeys, there was at least one cocaine dose that did not engender cocaine-appropriate responding during DD (i.e., <20\% cocaine-appropriate responding) yet functioned as a reinforcer during PR SA, suggesting that cocaine-like S(D) effects are not necessary for cocaine reinforcement. CONCLUSIONS: This within-subject model may provide new information related to the behavioral mechanisms of action leading to the high abuse potential of cocaine; such information may lead to novel pharmacological treatment strategies for addiction.}, address = {Department of Physiology and Pharmacology, Wake Forest University School of Medicine, 546 NRC, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.}, author = {Martelle, Jennifer L. and Nader, Michael A. }, citeulike-article-id = {3322437}, doi = {http://dx.doi.org/10.1007/s00213-008-1322-5}, issn = {0033-3158}, journal = {Psychopharmacology}, month = {September}, posted-at = {2008-09-23 16:51:49}, priority = {2}, title = {A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys.}, url = {http://dx.doi.org/10.1007/s00213-008-1322-5}, year = {2008} }

TY - JOUR ID - citeulike:3322437 L3 - citeulike-article-id:3322437 N2 - RATIONALE: Drug discrimination (DD) and drug self-administration (SA) are frequently used preclinical assays. All preclinical studies with cocaine have examined the discriminative stimulus (S(D)) and reinforcing (S(R)) effects in separate groups of subjects. OBJECTIVE: The objective of the study is to train drug-naïve rhesus macaques to discriminate self-administered cocaine from saline and to assess S(D) and S(R) effects using a within-subjects design. MATERIALS AND METHODS: Adult male rhesus monkeys (n = 4) were trained to self-administer cocaine (0.1 mg/kg per injection) under a progressive-ratio (PR) reinforcement schedule. Next, they were trained to discriminate self-administered cocaine (0.45 or 0.56 mg/kg) or saline under a fixed-ratio (FR) 50 schedule of food presentation. The final schedule combined DD and SA into a multiple [chained FR 50 SA (cocaine or saline), food-reinforced DD] and PR SA schedule. RESULTS: Each subject acquired SA under a PR schedule with significant differences in breakpoint between saline and cocaine evident by session 5. Self-administered cocaine was established as an S(D), such that 80% of responding before delivery of the first reinforcer and 90% of all responding occurred on the injection-appropriate lever. In all monkeys, there was at least one cocaine dose that did not engender cocaine-appropriate responding during DD (i.e., <20% cocaine-appropriate responding) yet functioned as a reinforcer during PR SA, suggesting that cocaine-like S(D) effects are not necessary for cocaine reinforcement. CONCLUSIONS: This within-subject model may provide new information related to the behavioral mechanisms of action leading to the high abuse potential of cocaine; such information may lead to novel pharmacological treatment strategies for addiction. JF - Psychopharmacology SN - 0033-3158 AD - Department of Physiology and Pharmacology, Wake Forest University School of Medicine, 546 NRC, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA. TI - A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys. AU - Martelle, Jennifer AU - Nader, Michael PY - 2008/09/21/ UR - http://dx.doi.org/10.1007/s00213-008-1322-5 ER -