The reinforcing effects of dopamine D1 receptor agonists in rhesus monkeys

Central dopaminergic systems have been implicated in the reinforcing effects of a number of stimuli, including drugs of abuse; however, the role of dopamine D1 receptors remains controversial. The present study evaluated the reinforcing effects of six reportedly selective D1 agonists of differing intrinsic efficacies. Rhesus monkeys with chronic intravenous catheters lever pressed on a fixed-ratio 10 schedule maintained by a base-line cocaine dose of 0.03 mg/kg/inj in daily 1-hr sessions. Periodically, D1 agonists were substituted for the cocaine base-line. All monkeys (n = 4) self-administered the high-efficacy D1 agonists SKF 81297, SKF 82958 and R(+) 6-Br-APB at rates above those maintained by vehicle; therefore, each of these compounds functioned as a positive reinforcer (maxima: SKF 81297: 55-172 inj/hr, 0.01 mg/kg/inj; R(+) 6-Br-APB:103-165 inj/hr, 0.001 mg/kg/inj; SKF 82958: 110-149 inj/hr, 0.01 mg/kg/inj). In contrast, no monkeys self-administered the lower-efficacy D1 agonists SKF 38393 (N = 4), SKF 77434 (N = 4) or the S(-) enantiomer of 6-Br-APB (N = 2). Additionally, two stimulant-naive monkeys acquired self-administration of SKF 81297. The finding that selective D1 receptor agonists can function as positive reinforcers implicates D1 receptors in the reinforcing effects of psychomotor stimulants and of other drugs that stimulate D1 receptors.