Abstract
Marked fluctuation of dopamine concentration in the striatum following long-term l-DOPA administration contributes to the development of l-DOPA-induced motor complications including l-DOPA-induced dyskinesias and wearing-off in patients with Parkinson's disease. We have shown that pretreatment with 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), a 5-HT 1A (5-hydroxytryptamine) receptor agonist, alleviates fluctuation of dopamine levels in the dopamine-denervated striatum of 6-hydroxydopamine-lesioned (hemiparkinsonian) rats after l-DOPA treatment. To determine whether co-administration of 8-OH-DPAT with l-DOPA prevents l-DOPA-induced motor complications, we examined rotation behavior and levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the striatum of 6-hydroxydopamine-lesioned rats treated with l-DOPA alone or l-DOPA + 8-OH-DPAT, twice daily, for 2 weeks. Co-administration of 8-OH-DPAT inhibited an increase of rotation behavior to l-DOPA and l-DOPA-induced increases in levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the dopamine-denervated striatum, both of which are established indices of l-DOPA-induced motor complications. These results suggest that pharmaceutical products that stimulate 5-HT 1A receptors could prove useful in prevention of the development of l-DOPA-induced motor complications in patients with Parkinson's disease.
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