Continuous amphetamine administration induces tyrosine hydroxylase immunoreactive patches in the adult rat neostriatum.

Continuous 3-day administration of d-amphetamine sulfate via a subcutaneous minipump induced the appearance of tyrosine hydroxylase immunoreactive patches in the neostriatum of adult Sprague-Dawley and Long-Evans rats at doses (greater than 20 mg/kg/day) that also produced axonal terminal degeneration as evidenced by Fink-Heimer silver grain deposition. The tyrosine hydroxylase patches coincided with striosomes identified by Leu-enkephalin immunoreactivity on adjacent sections. Sham-operated control, naive control, low dose amphetamine- (less than 15 mg/kg/day) and cocaine- (less than 125 mg/kg/day, IV) treated rats did not show tyrosine hydroxylase neostriatal patches nor axonal degeneration. These results suggest that the diffuse neostriatal dopamine system may be more susceptible to the neurotoxic, degenerative action of continuously administered amphetamine than is the islandic dopamine system.