Presynaptic inhibition of nigrostriatal dopamine release in the mouse: lack of cross tolerance between apomorphine, GBL and CGS 10746B.

Acute parenteral injections of apomorphine, gamma-butyrolactone (GBL) and CGS 10746B decreased dopamine release in the mouse nigrostriatal pathway as evidenced by decreases in striatal 3-methoxytyramine levels. In a 7 day treatment paradigm, the effects of acute apomorphine, GBL and CGS 10746B were unaltered in animals treated b.i.d. with GBL (500 mg/kg, i.p.). In contrast, the actions of acute CGS 10746B expressed a complete tolerance in mice treated b.i.d. with CGS 10746B (20 mg/kg, i.p.), while the actions of acute apomorphine or GBL were similar in the chronic saline and chronic CGS 10746 groups. These data show that the inhibition of striatal dopamine release by CGS 10746B is susceptible to tolerance. In addition, the lack of cross tolerance between GBL, apomorphine and CGS 10746B suggests independent sites of action for these agents in inhibiting dopamine release.