RT Journal Article SR Electronic T1 Effects of dopamine D1-like receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP JPET-AR-2021-000701 DO 10.1124/jpet.121.000701 A1 Paul W. Czoty A1 Michael A. Nader YR 2021 UL http://jpet.aspetjournals.org/content/early/2021/07/16/jpet.121.000701.abstract AB Although dopamine is known to play a prominent role in mediating the abuse-related effects of cocaine, the specific roles of dopamine receptor subtypes are not fully understood. Whereas the effects of drugs acting at dopamine D2-like receptors (D2R) have been characterized, less is known about dopamine D1-like receptors (D1R). The present experiments examined the effect of drugs with varying intrinsic efficacy at D1R on the relative reinforcing strength of cocaine in male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status influenced the behavioral effects of D1R-acting drugs. The high-efficacy D1R agonist SKF 81297, low-efficacy D1R agonist SKF 38393 and D1R antagonist SCH 23390 were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine choice dose-effect curve was determined daily. To assess selectivity of behavioral effects on cocaine choice, effects of doses that did not disrupt responding (indicated by a {greater than or equal to}35% decrease in total reinforcers delivered) were analyzed. Neither SKF 81297 nor SCH 23390 affected cocaine choice in dominant or subordinate monkeys. However, the low-efficacy agonist SKF 38393 selectively decreased cocaine choice; this effect was larger and only reached statistical significance in subordinate monkeys. Increasing the pretreatment time did not affect these results. The results indicate that, like D2R-acting drugs, the behavioral effects of D1R-acting drugs on cocaine choice can differ according to intrinsic efficacy and social status. Moreover, they demonstrate that D1R-acting drugs affect behavior under a narrower range of conditions than D2R-acting drugs. Significance Statement Cocaine use disorder remains a significant public health problem with no FDA-approved treatments. Although dopamine receptors have been strongly implicated in mediating the abuse-related effects of cocaine, the roles of dopamine receptor subtypes are incompletely understood. The present study in nonhuman primates found that cocaine choice was decreased only by a low-efficacy D1R agonist, and this effect was dependent on the social status of the monkey.