A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson's disease

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-HT1A (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-HT1A receptors could prove useful in prevention of the development Of L-DOPA-induced motor complications in patients with Parkinson's disease. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.