Minocycline restores striatal tyrosine hydroxylase in GDNF heterozygous mice but not in methamphetamine-treated mice.

Inflammation, phospho-p38 MAPK activation, and a reduction in glial cell line-derived neurotrophic factor (GDNF) occur in Parkinson's disease. Microglial activation in the substantia nigra and a tyrosine hydroxylase deficit in the striatum of 3-month-old GDNF heterozygous (GDNF(+/-)) mice were previously reported and both were exacerbated by a toxic methamphetamine binge. The current study assessed the effects of minocycline on these methamphetamine-induced effects. Minocycline (45 mg/kg, i.p.x 14 days post-methamphetamine or saline injections) reduced microglial activation and phospho-p38 MAPK in the substantia nigra of saline-treated GDNF(+/-) mice and in methamphetamine-treated wildtype and GDNF(+/-) mice. Although minocycline increased tyrosine hydroxylase-immunoreactivity in GDNF(+/-) mice, it did not attenuate the methamphetamine-induced reduction of tyrosine hydroxylase. The results suggest that neuroinflammation is deleterious to the dopamine system of GDNF(+/-) mice but is not the primary cause of methamphetamine-induced damage to the dopamine system in either GDNF(+/-) or wildtype mice.