Comparison of the reinforcing efficacy of two dopamine D2-like receptor agonists in rhesus monkeys using a progressive-ratio schedule of reinforcement

Abstract

High-efficacy D2-like dopamine (DA) receptor agonists can function as positive reinforcers when made available to animals for intravenous self-administration under a fixed-ratio (FR) schedule of reinforcement. In a previous study, however, low-efficacy D2-like agonists failed to maintain self-administration under an FR schedule, suggesting that agonist efficacy is directly related to efficacy as a positive reinforcer. To examine this hypothesis further, the present study compared two D2-like DA receptor agonists that maintained FR responding, but differ in their D2-like receptor efficacy and selectivity, using a procedure designed to rank-order drugs according to their efficacy as reinforcers. Rhesus monkeys ( n=5) were prepared with chronic, indwelling intravenous catheters and allowed to self-administer cocaine (0.1 mg/kg/injection) or saline on different days under a progressive-ratio (PR) schedule. When responding was stable, doses of the full D2-like agonist R(−)-propylnorapomorphine (NPA) or the partial D2-like agonist R(−)-apomorphine (APO) were made available for self-administration in the test sessions. Both compounds maintained self-administration with sigmoidal or biphasic dose–response functions. Surprisingly, the lower efficacy agonist APO was the more efficacious positive reinforcer. This result fails to support the hypothesis that D2-like receptor efficacy is directly related to efficacy as a reinforcer. It is possible that other pharmacological effects, e.g., D1 receptor activity, influenced self-administration.