%0 Journal Article
%T Dose-Dependent Effect of Flouxetine on 6-OHDA-Induced Catalepsy in Male Rats: A Possible Involvement of 5-HT1A Receptors
%A Hamdolah Sharifi
%A Alireza Mohajjel Nayebi
%A Safar Farajnia
%J Advanced Pharmaceutical Bulletin
%D 2013
%I Tabriz University of Medical Sciences
%R 10.5681/apb.2013.033
%X Purpose: Progressive loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson¡¯s disease (PD) leads to impairment of motor skills. Several evidences show that the role of serotonergic system in regulation of normal movement is pivotal and mediates via 5-HT1A receptors. Our previous study has shown that fluoxetine in acute injections able to attenuate catalepsy in 6-hydroxydopamine (6-OHDA)-lesioned rats. Since drugs are used chronically in clinic, in this study we attempted to evaluate effect of chronic administration of fluoxetine on 6-OHDA-induced catalepsy. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 ¦Ìg/2 ¦Ìl/rat) into the central region of SNc and assayed by using bar-test. Fluoxetine (1, 2.5, 5 and 10 mg/kg) was injected intraperitonealy (ip) for 10 days and its anti-cataleptic effect was assessed at the 10th day. Results: Fluoxetine in high doses (5 and 10 mg/kg) worsened 6-OHDA-induced catalepsy while it had anti-cataleptic effect at the dose of 1mg/kg. The anti-cataleptic effect of fluoxetine (1mg/kg) was reversed by co-administration with NAN-190 (0.5 mg/kg, ip), as a5-HT1Areceptor antagonist. Conclusion: According to the results it can be concluded that fluoxetine has anti-cataleptic effect in parkinsonian rats only at low doses, whereas at higher doses it worsens catalepsy. It¡¯s anti-cataleptic effect is exerted through affecting on 5-HT1Areceptors. However, at high doses other mechanisms may be involved. Further clinical studies are needed to prove it¡¯s possible clinical application as an adjuvant therapy in reducing catalepsy of PD.
%K Fluoxetine
%K 6-Hydroxydopamine
%K Catalepsy
%K Rat
%U http://journals.tbzmed.ac.ir/PDF/APB/Manuscript/APB-3-203.pdf