Modulation of the Reinforcing and Discriminative Stimulus Effects of Cocaine by the Dopamine D3 Receptor Partial Agonist CJB 090 [N‐(4‐(4‐(2,3‐Dichlorophenyl)piperazin‐4‐(pyridine‐2‐yl)benzamide] in Squirrel Monkeys

Abstract

Dopamine D3 receptor mechanisms have been implicated repeatedly in the behavioral effects of cocaine. This study evaluated the effects of the D3 receptor partial agonist CJB 090 in monkeys trained to: 1) discriminate cocaine from vehicle, 2) self‐administer cocaine on a second order fixed‐interval, fixed‐ratio schedule of i.v. drug injection or 3) self‐administer food on a comparable second order schedule of food delivery. In cocaine discrimination studies, CJB 090 did not substitute for cocaine, but significantly attenuated cocaine's discriminative stimulus effects when administered as a pretreatment. CJB 090 also significantly attenuated the partial cocaine‐like stimulus effects of the D3 receptor agonist PD128907, but enhanced the partial cocaine‐like stimulus effects of the D2 receptor agonist sumanirole. In self‐administration studies, CJB 090 did not attenuate responding maintained by i.v. injections of cocaine at a dose that reduced responding maintained by food. In a separate group of monkeys, observational tests revealed that CJB 090 did not induce scratching or biting (species‐typical effects of D2/3 receptor agonists) or catalepsy (typical effect of D2/3 receptor antagonists). The results provide little evidence that CJB 090 reduced cocaine's reinforcing effects. However they do suggest that CJB 090, acting primarily via a D3 receptor mechanism, antagonized the discriminative stimulus effects of cocaine at a dose that did not induce adverse observable effects.Supported by DA011054, NIDA‐IRP, RR00168. We thank J. Cao for CJB 090 synthesis.