Comparison of the reinforcing efficacy of two dopamine D2-like receptor agonists in rhesus monkeys using a progressive-ratio schedule of reinforcement.
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.
Woolverton
William L
WL
Department of Psychiatry and Human Behavior, Division of Neurobiology and Behavior Research, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. wwoolverton@psychiatry.umsmed.edu
Ranaldi
Robert
R
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012055:Reinforcement Schedule; D012646:Self Administration
C425777:10,11-dihydroxy-N-n-propylnorapomorphine; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D003042:Cocaine; D001058:Apomorphine