Effects of bremazocine on self-administration of smoked cocaine base and orally delivered ethanol,phencyclidine, saccharin,and food in rhesus monkeys: a behavioral economic analysis

There is increasing evidence that kappa-opioid receptor agonists modulate cocaine-maintained behavior, and limited findings implicate the involvement of kappa-opioid receptors in ethanol-maintained behaviors. The purpose of the present study was to investigate the effects of bremazocine, a kappa-opioid agonist, on the self-administration of smoked cocaine base and oral ethanol in rhesus monkeys (Macaca mulatta). To determine the selectivity of bremazocine, the effects of bremazocine pretreatment on the oral self-administration of phencyclidine (PCP), saccharin, and food were also examined. Adult male rhesus monkeys were trained to self-administer oral ethanol, PCP, saccharin (n = 8), food (n = 6), or smoked cocaine base (n = 6) and water during daily sessions. Bremazocine (0.00032-, 0.001-, and 0.0025-mg/kg i.m.) injections were given 15 min before session. The 4 days of stable behavior before pretreatment served as baseline. Demand curves (consumption x fixed ratio; FR) were obtained for smoked cocaine base, ethanol, and PCP by varying the cost (FR) of drug deliveries and measuring consumption (deliveries). Bremazocine (0.001 mg/kg) was administered at each FR value in nonsystematic order. Results indicate that bremazocine dose dependently reduced cocaine, ethanol, PCP, and saccharin intake. Food intake was affected less by bremazocine than the other substances in five of the six monkeys. Generally, bremazocine treatment reduced the demand for cocaine, ethanol, and PCP as well as other measures of response strength. These results extend the findings that kappa-agonists reduce the self-administration of drug and nondrug reinforcers to smoked cocaine base and oral ethanol, PCP, and saccharin in rhesus monkeys.