Effects of the novel dopamine D3 compound PG 619 on cocaine‐food choice in rhesus monkeys

Dopamine D 3 receptors are targets for cocaine pharmacotherapies. PG 619, which binds to D 3 receptors with ~100‐fold selectivity over D 2 receptors, elicited yawning similar to the D 3 agonist quinpirole only in monkeys with a cocaine self‐administration history. Furthermore, quinpirole, but not PG 619, reinstated cocaine seeking in the same monkeys and PG 619 attenuated cocaine‐primed reinstatement. The present study examined the acute and chronic (1‐ and 5‐days, respectively) effects of PG 619 (0.03–0.3 mg/kg, i.v., 10‐min presession) in adult male rhesus monkeys (n=4) self‐administering cocaine (sal, 0.01–0.3 mg/kg/inj) under a concurrent schedule with food reinforcement as the alternative. Under baseline conditions, cocaine choice increased in a dose‐dependent manner, with an ED 50 (± CI) of 0.017 (0.002) mg/kg. Acute PG‐619 resulted in rightward shifts in the cocaine dose‐response curve (for 0.3 mg/kg PG 619, the cocaine ED 50 = 0.09 ± 0.05 mg/kg) and 5 days of treatment produced even larger rightward shifts (ED 50 = 0.12 ± 0.02 mg/kg), with decreases in cocaine intake. These findings add to the growing data supporting the use of D 3 compounds as treatments for cocaine addiction.