THE REINFORCING EFFECTS OF DOPAMINE D1 RECEPTOR AGONISTS IN RHESUS-MONKEYS

Central dopaminergic systems have been implicated in the reinforcing e ffects 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 Dt agon ists of differing intrinsic efficacies. Rhesus monkeys with chronic in travenous catheters lever pressed on a fixed-ratio 10 schedule maintai ned by a base-line cocaine dose of 0.03 mg/kg/inj in daily 1-hr sessio ns. Periodically, D1 agonists were substituted for the cocaine base-li ne. All monkeys (n = 4) self-administered the high-efficacy D1 agonist s SKF 81297, SKF 82958 and R(+)6-Br-APB at rates above those maintaine d by vehicle; therefore, each of these compounds functioned as a posit ive 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-e fficacy D1 agonists SKF 38393 (N = 4), SKF 77434 (N = 4) or the S(-) e nantiomer of 6-Br-APB (N = 2). Additionally, two stimulant-naive monke ys acquired self-administration of SKF 81297. The finding that selecti ve D1 receptor agonists can function as positive reinforcers implicate s D1 receptors in the reinforcing effects of psychomotor stimulants an d of other drugs that stimulate D1 receptors.