Short-term and long-term effects of methamphetamine on biogenic amine metabolism in extra-striatal dopaminergic nuclei

Abstract

The effects of multiple toxic doses of methamphetamine on catecholaminergic, serotonergic and cholinergic metabolism in the neostriatum, nucleus accumbens, olfactory tubercle and median eminence area of the rat brain have been investigated. Methamphetamine (15 mg/kg s.c.) was administered every 6 hr for 5 doses. Thirty-six hours after the first of 5 doses, tyrosine hydroxylase (TH) activity, as well as dopamine and norepinephrine levels, were significantly decreased in the neostriatum and olfactory tubercle but were not altered in the nucleus accumbens or median eminence area. Prior to the 36-hr time point, drug treatment significantly decreased TH activity in the neostriatum and olfactory tubercle, but did not change the enzyme activity in the nucleus accumbens. Neostriatal TH activity in the neostriatum and olfactory tubercle was significantly decreased up to 30 days after methamphetamine. However, only a slight change in TH activity occurred in the nucleus accumbens at 30 days after drug treatment. In contrast, tryptophan hydroxylase (TPH) activity was significantly decreased from 3 hr after the first dose up to 30 days after the fifth dose in all brain regions investigated. Methamphetamine caused a slight decrease in choline acetyltransferase activity only in the olfactory tubercle at the 36-hr time point. This evidence suggests that the serotonergic neurons are more sensitive to the toxic effects of methamphetamine than the dopaminergic neurons, whereas, the cholinergic neurons seem to be essentially unaffected.