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

Dopamine D3 receptors are targets for cocaine pharmacotherapies. PG 619, which binds to D3 receptors with ~100‐fold selectivity over D2 receptors, elicited yawning similar to the D3 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 ED50 (± 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 ED50 = 0.09 ± 0.05 mg/kg) and 5 days of treatment produced even larger rightward shifts (ED50= 0.12 ± 0.02 mg/kg), with decreases in cocaine intake. These findings add to the growing data supporting the use of D3 compounds as treatments for cocaine addiction.