title: 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.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D000068180:Aripiprazole; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D004291:Dominance-Subordination; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D005247:Feeding Behavior / Q000187:drug effects*; D008024:Ligands; D008252:Macaca fascicularis; D008297:Male; D010879:Piperazines / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D015363:Quinolones / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000068180:Aripiprazole; D003042:Cocaine