D3 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.