Reduced apomorphine sensitivity of dopamine metabolism in rat striatum after repeated administration of methamphetamine.

Rats received daily injections of saline or methamphetamine (MAP; 4 mg/kg/day) for 14 days. Seven days after the completion of this regime, dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in the striatum following intraperitoneal injections of either saline plus gamma-butyrolactone (GBL; 750 mg/kg) or apomorphine (2 mg/kg) plus GBL. The saline plus GBL challenges produced no difference in the DA or DOPAC levels between saline- and MAP-treated rats. By contrast, the apomorphine plus GBL challenges produced higher DOPAC levels in MAP-treated rats than saline-treated rats, although they produced no difference in the DA levels between the two groups. These results indicate that apomorphine depresses the striatal DA metabolism less in MAP-treated rats than in saline-treated control rats. Repeated MAP administration might produce this effect through apomorphine subsensitivity of presynaptic DA autoreceptors.