Drug-induced rotation intensity in unilateral dopamine-depleted rats is not correlated with end point or qualitative measures of forelimb or hindlimb motor performance

Abstract

The pharmacological induction of rotational (circling) behavior is widely used to assess the effects of lesions to the dopaminergic system and the success of treatment strategies in rat models of Parkinson’s disease. While the number of rotations under apomorphine, L-DOPA and amphetamine is related to the extent of dopamine depletion after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system, the relationship of the intensity of rotational behavior to the degree of impairment in motor behavior is unclear. The present study examined this question by correlating rotational behavior and motor abilities in a rat analogue for Parkinson’s disease produced by unilateral nigrostriatal bundle lesion with 6-hydroxydopamine. Ipsiversive and contraversive rotation was measured in the rats following systemic administration of low and high doses of apomorphine, the dopamine precursor L-DOPA, and amphetamine. The motor assessment included end point and qualitative measures of fore- and hindlimbs assessed in a skilled reaching task and a skilled ladder rung walking task. The intensity of drug-induced rotation did not correlate with the measures of motor performance. We conclude that independence of rotational behavior and motor performance argues that both the assessment of 6-hydroxydopamine behavioral deficits and potential treatments for the functional deficits require comprehensive assessment, including both measures of rotation and motor behavior.