Factors in amphetamine-induced contralateral rotation in the unilateral 6-OHDA lesion rat model during the first-week postoperative: implications for neuropathology and neural grafting

Abstract

Amphetamine induced ipsilateral rotation in rats with chronic unilateral 6-hydroxydopamine (6-OHDA) lesions is a widely accepted line of evidence supportive of dopaminergic mediation of amphetamine effects on motoric behavior. However, there is literature indicating that amphetamine induces contralateral rotation, in the early postoperative phase of a unilateral 6-OHDA lesion. In an attempt to reconcile these opposite amphetamine effects on rotation in terms of dopaminergic mechanisms, a series of 4 experiments were conducted. These studies showed that amphetamine reliably elicits contralateral rotation for up to 7 days postoperative but only ipsilateral rotation thereafter. The amphetamine induced contralateral rotation differed behaviorally in several respects from subsequent ipsilateral rotation induced by amphetamine. It was comparatively more intense; and, while onset of peak rotation was dose dependent, rate of rotation was independent of dose level (0.5, 1.0 and 2.5 mg/kg). Dopamine and dopamine metabolite analyses by HPLC-EC after 3 postperative intervals (days 3, 6, and 9) indicated a progressive and severe depletion of striatal dopamine in conjunction with elevated dopamine turnover. Importantly, after 6 days postoperative, dopamine was reduced to <0.06% after intact hemisphere but yet, amphetamine (1.0 mg/kg) elicited contralateral rotation. It was proposed that amphetamine could release a small amount of dopamine present in a sparse number of residual degenerating terminals and this dopamine, unrestricted by reuptake, could widely access supersensitive dopamine receptors to elicit contralateral rotation. This possibility calls into question amphetamine tests for neural graft efficacy in animal models which use amphetamine induced contralateral rotation as the criterion response.