Effects of chronic methamphetamine on the nigral-striatal dopamine system in rat brain: tyrosine hydroxylase immunochemistry and quantitative light microscopic studies.

Chronic administration of methamphetamine (20 mg/kg, IP, every 12 hours for 10 days) produced a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the caudate nucleus in rats when examined 60 days following the final methamphetamine injection. This effect was quantitated using the Leitz Data Acquisition and Display System (DADS) revealing that there was a 74% decrease in tyrosine hydroxylase positive processes in the caudate nucleus. Furthermore, this treatment also produced a large decrease in the number of tyrosine hydroxylase positive staining neuronal perikarya in the pars compacta of the substantia nigra. This effect was also quantitative using the Leitz-(DADS) system, revealing a decrease of 89% in tyrosine hydroxylase positive material. These data demonstrate that chronic administration of methamphetamine produces a long-term loss of tyrosine hydroxylase enzyme in both the cell bodies of the substantia nigra and the nerve terminals in the caudate nucleus. Whether this effect is due to the degeneration of the neurons or some metabolic effect remains to be determined.