PROTECTIVE EFFECTS OF PERGOLIDE ON DOPAMINE LEVELS IN THE 6-HYDROXYDOPAMINE-LESIONED MOUSE-BRAIN

Pergolide, along with bromocriptine and lisuride, is one of the most a ctive dopamine receptor agonists. To determine whether or not pergolid e protects against dopaminergic neuronal damage, via its activity on m onoamine metabolism, we studied the effects of pergolide pretreatment on changes in monoamines and their metabolites in the mouse striatum a fter intracerebroventricular injection of 6-hydroxydopamine with pretr eatment of desipramine. After intracerebroventricular administration o f 6-hydroxydopamine (40 mu g) in mice, the levels of dopamine and its metabolites (DOPAC, HVA) in the striatum rapidly decreased to 49%, 29% and 68%, respectively, of the naive controls at week 1 but then gradu ally recovered to control levels at weeks 2 and 4. Repeated pretreatme nt with pergolide (0.5 mg/kg, i.p.) for 7 days before administration o f 6-hydroxydopamine, almost completely protected against reduction in striatal dopamine and its metabolites 1 week after injection of 6-hydr oxydopamine. Therefore, pergolide could normalize the decreased dopami ne synthesis or storage, and has a neuroprotective effect against dopa minergic dysfunction induced by the neurotoxin, 6-hydroxydopamine. Alt hough we found that pergolide did not show radical scavenging activity in an in vitro system that generated hydroxyl radicals, it has been r eported in vivo that pergolide treatment may induce Cu/Zn superoxide d ismutase in the rat striatum. Considering these findings, pergolide ma y well be protective to dopaminergic neurons, largely because of its e ffects on presynaptic autoreceptors and on its induction of Cu/Zn supe roxide dismutase. Further research on the neuroprotective effects of p ergolide in Parkinson disease models, by injection of 6-hydroxydopamin e, is needed to clarify its mechanism of action on dopaminergic indice s.