Kazuyoshi Takamuki

Enhancement of dopamine release from striatal slices of rats that were subchronically treated with methamphetamine.

The effect of dopamine (DA) uptake inhibitors (methamphetamine, nomifensine, and phenylethylamine) on the release of endogenous DA from striatal slices of rats pretreated with methamphetamine (6 mg/kg/day for 9 days) was investigated. The exposure of methamphetamine-pretreated rat striatal slices to a low concentration (10(-7) M, 5 X 10(-7) M) of methamphetamine caused a greater increase in DA efflux than that of saline-treated rat striatal slices. The drug-treated rats displayed an enhanced stereotyped behavioral response to a small dose of methamphetamine (1 mg/kg). Removal of Ca2+ from the superfusion medium did not affect the difference in the rates of methamphetamine (10(-7) M) induced DA release between methamphetamine-treated and saline-treated rat striatal slices. Nomifensine- and phenylethylamine-induced DA release from striatal slices was also enhanced by repeated administration of methamphetamine. On the other hand, there was no difference in K+-induced DA release between the two groups. Moreover, repeated administration of methamphetamine caused a significant increase in 3H-dopamine uptake in rat striatal synaptosomes. These results suggest that the behavioral sensitization produced by the repeated administration of methamphetamine is accompanied by an enhancement in the release of DA induced by methamphetamine, nomifensine, and phenylethylamine in vitro and is also accompanied by increased DA uptake into striatal synaptosomes.