Long-lasting decrease in dopamine uptake sites following repeated administration of methamphetamine in the rat striatum.

We investigated the effects of repeated administration of methamphetamine on dopamine (DA) uptake sites in the rat striatum by using an increasing dose paradigm of methamphetamine (2.5 mg/kg on day 1; 5 on day 3; 7.5 on day 5 and 10 on day 7), each being given twice on the indicated day by s.c. injection. It has been established that this administration paradigm produces distinct sensitization in methamphetamine-induced behavior. A 36% reduction in specific [3H]DA uptake, and a 29% reduction in specific [3H]GBR12935 binding in the striatum were demonstrated in rats sacrificed 7 days after the last methamphetamine administration. A similar reduction in striatal [3H]GBR12935 binding sites was observed even 30 days after discontinuation of the drug. These data indicate that this treatment regimen of gradually escalating doses of methamphetamine induces a long-lasting decrease of DA uptake sites in rat striatum.