Effects of high-dose methamphetamine administration on serotonin uptake sites in rat brain measured using [3H]cyanoimipramine autoradiography.

Repeated administration of high doses of methamphetamine (15 mg/kg given for 5 doses over 24 h) resulted in long-term decreases in the binding of [3H]cyanoimipramine ([3H]CN-IMI) to serotonin uptake sites measured using quantitative autoradiography. Seven days after termination of drug administration decreases were seen in 23 of 28 regions examined. This is consistent with previous studies indicating that methamphetamine and related amphetamines are neurotoxic to serotonin neurons. Significant decreases were still present in many brain areas on the same dosage schedule 30 days after drug administration. However, the number of areas affected was considerably less, consistent with some regrowth of serotonin neurons. At a lower dosage (7.5 mg/kg on the same schedule) no effects on [3H]CN-IMI binding were seen. The results of this study provide support for the serotonergic neurotoxicity of repeated methamphetamine administration in rats. They also show that the neurotoxicity is highly regional and dose dependent.