Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
11030742 | Progress in Neuro-Psychopharmacology and Biological Psychiatry | 2019 | 7 Pages |
Abstract
Methamphetamine, an amphetamine derivative, is a powerful psychomotor stimulant and commonly used drug of abuse. This study examined the effect of binge-like methamphetamine (MA) dosing (4â¯Ãâ¯4â¯mg/kg, s.c., 2â¯h apart) on regional dopamine and dopaminergic metabolite levels in rat brain at a range of early time points after final dose (2-48â¯h). Body temperature was elevated when measured 2â¯h after the last dose. MA increased dopamine levels in the frontal cortex 2 and 24â¯h after the last dose. The dopamine level was also increased in the amygdala at 24â¯h. No change was observed in the striatum at any time point, but levels of the dopamine metabolite DOPAC were markedly reduced at 24 and 48â¯h. Tyrosine hydroxylase expression is induced downstream of dopamine activity, and it is the rate limiting enzyme in dopamine synthesis. The effect of MA binge-like dosing on the volume of tyrosine hydroxylase containing cell bodies and the area fraction of tyrosine hydroxylase containing fibres was also assessed. MA increased the area fraction of tyrosine hydroxylase fibres in the frontal cortex and reduced the volume of tyrosine hydroxylase containing cell bodies 2â¯h after last dose in the ventral tegmental area and the substantia nigra. An increase in cell body volume in the substantia nigra was observed 48â¯h after treatment. These findings collectively highlight the importance of the dopaminergic system in methamphetamine induced effects, identify the frontal cortex, amygdala and striatum as key regions that undergo early changes in response to binge-like methamphetamine dosing and provide evidence of time-dependent effects on the cell bodies and fibres of tyrosine hydroxylase expressing neurons.
Related Topics
Life Sciences
Neuroscience
Biological Psychiatry
Authors
Andreia Moreira da Silva Santos, John P. Kelly, Peter Dockery, Karen M. Doyle,