Effects of dopamine D2/D3 receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys.

Abstract

Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence. The present experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine. Use of socially housed cynomolgus monkeys permitted the assessment of whether social status, known to alter D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds. The high-efficacy agonist R(-)-norpropylapomorphine [(-)-NPA], low-efficacy agonist aripiprazole (ARI), and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily. The effects of 5-day treatment with ARI and (-)-NPA were characterized under conditions in which monkeys did (ARI) or did not [ARI and (-)-NPA] self-administer cocaine during treatment. When administered acutely, ARI and ETIC increased the choice of low cocaine doses, and only (-)-NPA decreased the choice of higher cocaine doses and cocaine intake; effects were similar across social ranks. When administered repeatedly while self administration occurred only on days 1 and 5 of treatment, ARI, but not (-)-NPA, decreased cocaine choice in dominant monkeys, whereas (-)-NPA, but not ARI, did so in subordinates. When dominant monkeys self-administered cocaine on all five days of ARI treatment, however, these effects were not observed. The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics. Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.

• Authors: Paul W Czoty, Michael A Nader
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 344 Issue 2 Pg. 329-38 (Feb 2013) ISSN: 1521-0103 [Electronic] United States
• PMID: 23211363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Dopamine Agents
• Dopamine D2 Receptor Antagonists
• Ligands
• Piperazines
• Quinolones
• Receptors, Dopamine D2
• Receptors, Dopamine D3
• Aripiprazole
• Cocaine

Topics

• Animals
• Aripiprazole
• Choice Behavior (drug effects)
• Cocaine (administration & dosage, metabolism)
• Cocaine-Related Disorders (metabolism, prevention & control, psychology)
• Dominance-Subordination
• Dopamine Agents (metabolism, pharmacology, therapeutic use)
• Dopamine D2 Receptor Antagonists
• Dose-Response Relationship, Drug
• Drug Partial Agonism
• Feeding Behavior (drug effects)
• Ligands
• Macaca fascicularis
• Male
• Piperazines (agonists, pharmacology, therapeutic use)
• Quinolones (agonists, pharmacology, therapeutic use)
• Receptors, Dopamine D2 (agonists)
• Receptors, Dopamine D3 (agonists, antagonists & inhibitors)
• Reinforcement, Psychology
• Self Administration