| Abstract: | Two separate experiments were conducted to assess the behavioral and biochemical effects of chronicl-dihydroxyphenylalanine (l-DOPA) treatment in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. In this animal model, contralateral rotation provides the behavioral indicator response forl-DOPA activation of the dopamine denervated striatum. Following 30 dailyl-DOPA treatments, a subthreshold dose (10 mg/kg) for rotation became suprathreshold and the contralateral rotation induced by a suprathreshold dose (20 mg/kg) became exaggerated. This motoric sensitization tol-DOPA was not reversed by a three-day period ofl-DOPA withdrawal. In contrast with the emergence of behavioral sensitization tol-DOPA, biochemical measurements showed that the increase of dopamine metabolite concentrations (DOPAC and HVA) induced by acutel-DOPA treatment became attenuated with chronic treatment. This finding suggests that chronicl-DOPA treatment produces a partial tolerance in the conversion ofl-DOPA to extracellular dopamine. The emergence ofl-DOPA sensitization-overstimulation effects was hypothesized to reflect the combined effects of dopamine receptor priming and Pavlovian drug conditioning and to contribute to the emergence of dyskinetic effects ofl-DOPA therapy. The partial tolerance observed for dopamine metabolites was hypothesized to represent a decreased conversion ofl-DOPA to dopamine which with long-term treatment could progress to an eventual wearing-off effect ofl-DOPA therapy. |
