Dose-Dependent Effect of Flouxetine on 6-OHDA-Induced Catalepsy in Male Rats: A Possible Involvement of 5-HT1A Receptors
Journal Title: Advanced Pharmaceutical Bulletin - Year 2013, Vol 3, Issue 1
Abstract
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 μg/2 μl/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.
Authors and Affiliations
Hamdolah Sharifi, Alireza Mohajjel Nayebi, Safar Farajnia
Keywords
Related Articles
- EP ID EP93285
- DOI 10.5681/apb.2013.033
- Views 141
- Downloads 0
Short Term Administration of L-Carnitine Can Be Detrimental to the Ischemic Heart
Previous studies have shown that L-carnitine (LC) supplementation may exert a cardioprotective effect in cardiomyopathy, prevent arrhythmias in myocardial infarction and increase exercise tolerance in angina. Interesting...
Comparison of in Vitro Activity of Doripenem versus Old Carbapenems against Pseudomonas Aeruginosa Clinical Isolates from both CF and Burn Patients
Purpose: The antimicrobial activity of doripenem in comparison of imipenem, meropenem and ertapenem among Pseudomonas aeruginosa isolated from burn and Cystic Fibrosis (CF) patients were determined. Methods: Metallo-β-la...
Application of lactobionic acid and nonionic surfactants as solubilizing agents for parenteral formulation of clarithromycin
Purpose: The purpose of this paper is to enhance the solubility of clarithromycin (CLR) using nonionic surfactants and some type of acids for preparation of the new formulations. Methods: Myrj 52 and chremophor (2.5 and...
Affinity Purification of Tumor Necrosis Factor-α Expressed in Raji Cells by Produced scFv Antibody Coupled CNBr-Activated Sepharose
Purpose: Recombinant tumor necrosis factor-alpha (TNF-α) has been utilized as an antineoplastic agent for the treatment of patients with melanoma and sarcoma. It targets tumor cell antigens by impressing tumor-associated...
Modified Synthesis of Erlotinib Hydrochloride
Purpose: An improved and economical method has been described for the synthesis of erlotinib hydrochloride, as a useful drug in treatment of non-small-cell lung cancer. Methods: Erlotinib hydrochloride was synthesized in...