Changes in sensitivity of dopamine autoreceptors in rat striatum after subchronic treatment with methamphetamine

To determine the functional alterations of the release modulating striatal dopamine (DA) autoreceptors that might be associated with the behavioral sensitization to methamphetamine after pretreatment with methamphetamine, we investigated the effect of apomorphine and sulpiride on electrically evoked DA release from striatal slices of rats pretreated with methamphetamine. Apomorphine induced a dose-dependent inhibition of the DA release evoked from the striatal slices. Pretreatment with methamphetamine (6 mg/kg per day for 9 days) significantly reduced the inhibitory effect of apomorphine. On the other hand, sulpiride caused a dose-dependent increase in the DA release evoked from the striatal slices. The enhancement by sulpiride of the evoked DA release was diminished by pretreatment with methamphetamine. These results show that pretreatment with methamphetamine blunts the responsiveness of evoked DA release to the DA antagonists as well as to the DA agonists, indicating that DA autoreceptor subsensitivity is produced by pretreatment with methamphetamine.