Elsevier

Neuropharmacology

Volume 20, Issue 12, December 1981, Pages 1135-1140
Neuropharmacology

Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain

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Abstract

Repeated administration of methamphetamine for 30 hr produced large decreases in the activity of tryptophan hydroxylase and in the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in several serotonergic nerve terminal regions of the rat brain. Six sequential doses of methamphetamine (15 mg/kg, s.c.), given every 6 hr, produced a differential regional reduction in the levels of 5-HT, 5-HIAA and in tryptophan hydroxylase activity. Among the regions tested, the neostriatum and cerebral cortex were most affected and the hypothalamus was least affected. A significant recovery in the levels of 5-HT, 5-HIAA and tryptophan hydroxylase activity had occurred by 10 days following drug treatment. Recovery of enzyme activity in the hypothalamus, spinal cord and olfactory tubercle was complete, whereas enzyme activity was still significantly depressed in the neostriatum, nucleus accumbens, cerebral cortex and hippocampus. Similar trends were obtained for 5-HT and 5-HIAA. Tryptophan levels in some regions were increased at 36 hr and remained elevated 110 days after methamphetamine treatment.

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