D-3 receptor test in vitro predicts decreased cocaine self-administration in rats

THE three dopamine agonists with highest reported D-3 receptor selectivity in vitro, pramipexole, quinelorane and PD128,907, decreased self-administration of a high dose of cocaine in rats as a result of a leftward shift in the cocaine dose-effect function. In contrast the D-3 preferring antagonist nafadotride increased cocaine self-administration. Moreover the relative potencies of these and other D-2-like dopamine agonists (lisuride, 7-OH-DPAT, quinpirole, apomorphine, bromocriptine) to modulate cocaine self-administration were highly correlated with their relative potencies for increasing mitogenesis in vitro in cell lines expressing D-3 but not D-2 receptors. These results support the hypothesis that the D-3 receptor may be an important target for pharmacotherapies for cocaine abuse and dependence.