Rats with Partial Unilateral Nigrostriatal Lesions as a Model for Studying CNS Plasticity

Abstract

We describe the methods and rationale for using rats with a partial unilateral lesion of the nigrostriatal system as an animal model for studying neural plasticity in both young and aged brains. The rats are lesioned with 6-hydroxydopamine injected into the substantia nigra or the medial forebrain bundle. Amphetamine- and apomorphine-induced rotational behaviors are tested 3 and 4 weeks following the lesion. Based on the rotational responses to amphetamine and apomorphine administration, animals can be classified into one of three groups: unaffected, partially lesioned, or severely lesioned. Animals classified as displaying unaffected rotational behavior are those that do not respond to either amphetamine or apomorphine stimulation. Partially lesioned animals rotate ipsilateral to the lesioned side upon amphetamine injection, but do not display a significant number of rotations in response to apomorphine administration. In contrast, severely lesioned rats rotate after both amphetamine and apomorphine injections. Cell counts reveal that the mean number of dopamine neurons in the ventral mesencephalon of partially lesioned animals is reduced to 40% of that of the intact side. Also in partially lesioned animals, dopamine concentrations on the lesion side are even more severely depleted, averaging about 20% of levels in the contralateral intact striatum. Striatal dopamine concentrations correlate well with the number of surviving dopamine neurons in the ventral mesencephalon (r² = 0.66, P < 0.05). Amphetamine-induced rotation rates also show a moderate correlation with both striatal dopamine concentrations and mesencephalic dopamine neuron cell counts. Therefore, rotational behavior induced by amphetamine and apomorphine stimulation can be used to identify partially lesioned rats following unilateral 6-hydroxydopamine lesions. It is also possible to estimate the extent of nigrostriatal system damage from the rate of amphetamine-induced rotation.