Bromocriptine markedly suppresses levodopa-induced abnormal increase of dopamine turnover in the Parkinsonian striatum

Bromocriptine, a dopamine agonist, is commonly used in combination with levodopa for the treatment of Parkinson's disease (PD). To investigate the theoretical basis of such combination therapy, we examined the effects of bromocriptine administered alone or in combination with levodopa on dopamine turnover in the striatum of hemi-parkinsonism rats. The parkinsonian striatum showed a 3.4-fold increase of dopamine turnover relative to the control striatum, as often observed in the brain of PD patients. A 7-day course of levodopa therapy markedly increased dopamine turnover in the parkinsonian striatum (53-fold of control level) than in the control striatum (5-fold of the control level). However, bromocriptine specifically and markedly suppressed the levodopa-induced abnormal activation of dopamine turnover in the Parkinsonian striatum. Our findings explain the pharmacological basis for the introduction of bromocriptine during long-term levodopa therapy.