Tyrosine hydroxylase immunochemistry and quantitative light microscopic studies of the mesolimbic dopamine system in rat brain: effects of chronic methamphetamine administration.

Long-term treatment of rats with methamphetamine (20 mg/kg, IP, every 12 hours for 10 days) resulted in a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the nucleus accumbens and frontal cortex, as well as the ventral tegmental area of the midbrain, when examined 60 days following termination of the drug treatment regimen. Quantitative analysis showed a 71 and 78% decrease in tyrosine hydroxylase staining processes in the nucleus accumbens and frontal cortex, respectively, and a 90% decrease in tyrosine hydroxylase positive material in the ventral tegmental area. Thus, tyrosine hydroxylase enzyme in both the cell bodies of the midbrain ventral tegmental area as well as in the nerve terminals in post-synaptic target regions of the forebrain is depleted by chronic methamphetamine administration.