Deficits in instrumental responding after 6-hydroxydopamine lesions of the nigro-neostriatal dopaminergic projection

Abstract

Rats subjected to bilateral injections of 6-hydroxydopamine (8 μg) into the zona compacta of the substantia nigra completely failed to learn either a one-way active avoidance response or a simple approach response for food reinforcement. The neurotoxic lesions reduced striatal dopamine and tyrosine hydroxylase activity to less than 10 percent of control levels. A significant loss of hypothalamic norepinephrine was also produced by these lesions suggesting that this procedure also destroyed part of the ventral noradrenergic bundle. When bilateral lesions of the latter pathway were made caudal to the substantia nigra, so that similar losses were produced in hypothalamic norepinephrine levels without reducing striatal tyrosine hydroxylase activity, normal acquisition of both avoidance and appetitive responses were observed. In another experiment, almost complete retention of avoidance responding was obtained if the animals were overtrained on this response prior to the bilateral nigral lesions. These results suggest that the nigro-neostriatal dopaminergic projection may play an important role in the acquisition of learned instrumental responses.