Inhibitory effect of a selective kappa receptor agonist, U-50, 488H, on methamphetamine-elicited ipsilateral circling behavior in rats with unilateral nigral lesions.

The present study was designed to investigate the effect of U-50, 488H, a highly selective kappa opioid agonist, on ipsilateral and contralateral circling behavior induced by methamphetamine and by apomorphine, respectively. U-50, 488H (3.2-10 mg/kg IP) by itself failed to induce either ipsilateral or contralateral circling in rats with unilateral nigral lesions produced by an injection of 6-hydroxydopamine. U-50, 488H produced a significant dose-dependent inhibition of methamphetamine (1.0 mg/kg SC)-elicited ipsilateral circling. However, it had no effect on contralateral circling induced by apomorphine (0.5 mg/kg SC). The present results indicate that U-50, 488H presynaptically inhibits the release of dopamine in the rat striatum.