Buspirone improves the anti-cataleptic effect of levodopa in 6-hydroxydopamine-lesioned rats

In parkinson's disease (pd),prolonged exposure to l-3,4- dihydroxyphenylalanine (l-dopa) results in motor fluctuations,such as the on-off phenomenon,and l-dopa-induced dyskinesia. previously,we found that activation of 5-ht1a in the substantia nigra pars compacta (snc) decreased catalepsy in parkinsonian rats. in the current investigation,we attempted to evaluate the effect of buspirone on the anti-cataleptic effect of l-dopa in 6-hydroxydopamine (6-ohda)-lesioned male wistar rats. catalepsy was induced by the unilateral infusion of 6-ohda(8 μg/2 μl/rat) into the central region of the snc. after a 3-week recovery period,rats received l-dopa intraperitoneally (ip; 15 mg/kg) twice daily for 20 days,and the anti-cataleptic effect of l-dopa was assessed by the bar test at days 5,10,15 and 20. the results showed that l-dopahad an anti-cataleptic effect only until day 15,and its effect was abolished on day 20. on day 21,these rats were co-treated with three different doses of buspirone (0.1,0.5 and 2.5 mg/kg,ip) and l-dopa(15 mg/kg,ip). at a dose of 0.5 mg/kg,buspirone improved the anti-cataleptic effect of l-dopa. furthermore,the effect of buspirone (0.5 mg/kg,ip) on the anti-cataleptic effect of l-dopa (15 mg/kg,ip) was reversed by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine hydrobromide (nan-190; 0.5 mg/kg,ip),a 5-ht1a receptor antagonist. from these results,it may be concluded that buspirone improves the anti-cataleptic effect of l-dopain a 6-ohda-induced animal model of pd through the activation of 5-ht1a receptors. in this regard,further investigations should be undertaken to clarify the exact mechanism of the interaction between 5-ht1a and dopaminergic neurons. copyright © 2011 by institute of pharmacology polish academy of sciences.