Behavioral and biochemical evidence for a different effect of repeated administration of l-DOPA and bromocriptine on denervated versus non-denervated striatal dopamine receptors

Abstract

The effect of repeated administration of bromocriptine and l-3,4-dihydroxyphenylalanine ( l-DOPA) was studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Groups of rats injected eight times with bromocriptine or l-DOPA significantly increased their contraversive circling. Rats receiving only two injections of bromocriptine did not. Animals receiving two injections of l-DOPA showed a slight but significant increase in circling. The affinity of the binding of [ 3H]spiperone to the dopamine receptors was unchanged by the lesion or the treatments, while the density of the binding was significantly modified. Chronic treatment with bromocriptine induced a significant decrease in the density of D 2 dopamine receptors in the intact striata, while on the lesioned side, it remained unchanged. By contrast, chronic administration of l-DOPA induced a significant increase in density of the striatal dopamine receptors in the lesioned striata in addition to that caused by denervation, while the decrease on the intact side was not significant. It seems that contrary to the intact striatum, the lesioned side had a defective down-regulation mechanism in response to chronic treatment with a dopamine agonist. The results also show that l-DOPA was more potent than bromocriptine in inducing agonist supersensitivity in a denervated striatum. This may explain why chronic treatment with bromocriptine has a lesser tendency to induce dyskinesia in patients with Parkinson's disease.