PT  - JOURNAL ARTICLE
AU  - Paul W. Czoty
AU  - Michael A. Nader
TI  - Effects of dopamine D2/D3 receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys
AID  - 10.1124/jpet.112.201012
DP  - 2012 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.112.201012
4099  - http://jpet.aspetjournals.org/content/early/2012/12/04/jpet.112.201012.short
4100  - http://jpet.aspetjournals.org/content/early/2012/12/04/jpet.112.201012.full
AB  - Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence. These 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 the whether social status, known to influence 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 choice of low cocaine doses and only (-)-NPA decreased 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 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.