Neurochemical correlates of sparing from motor deficits in rats depleted of striatal dopamine as weanlings.

Abstract

The behavioral and neurochemical effects of striatal DA depletions were investigated in rats lesioned as weanlings (Day 27) or as adults (250-300 g). Administration of 6-OHDA into the medial forebrain bundle resulted in comparably large (> or = 95%) depletions of tissue levels of DA in both age groups. As expected, rats depleted of DA as adults exhibited marked deficits in motoric behavior and body weight regulation that persisted for the 8 days of postsurgical observation. In contrast, rats depleted of DA as weanlings were spared from such deficits, and their behavior closely resembled that of age-matched controls. Microdialysis studies revealed dialysate levels of striatal DA that paralleled these age-dependent behavioral differences. At a time when age-related behavioral differences were still quite pronounced (5-6 days postsurgery), basal DA levels were reduced by 80% of control values in rats lesioned as adults whereas basal DA levels in rats lesioned as weanlings were unchanged relative to their controls. Finally, adults depleted of striatal DA as weanlings were no more sensitive to the movement-impairing effects of intrastriatal sulpiride (3.0 or 10.0 micrograms/hemisphere) infusions than were control rats. These data suggest that weanlings compensate for large, but incomplete, denervation of striatal DA with markedly enhanced release and turnover from residual terminals. This developmental plasticity may prevent the occurrence of behavioral deficits soon after the lesion and also the supersensitivity to the challenging effects of DA antagonists as animals grow into adulthood.