Reversal of haloperidol-induced orofacial dyskinesia by quercetin, a bioflavonoid.
BACKGROUND
Tardive dyskinesia is a serious neurological syndrome associate with long-term administration of neuroleptics to humans and experimental animals. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. Quercetin is a bioflavonoid with strong antioxidant properties.


OBJECTIVE
To evaluate the effect of chronic quercetin treatment on haloperidol-induced orofacial dyskinesia.


METHODS
Vacuous chewing movements (VCM) in rats, a widely accepted animal model of tardive dyskinesia was employed in the present study. VCM were induced in rats by daily administration of haloperidol (1.0 mg/kg) for a period of 21 days. Animals with established dyskinesia were given quercetin for a period of 4 weeks and behavioral scoring was recorded every week before administration of quercetin. Animals were killed after the last behavioral recordings and biochemical estimations were carried out.


RESULTS
Chronic haloperidol (1.0 mg/kg for 21 days) treatment significantly induced VCM and tongue protrusions in rats and quercetin (25-100 mg/kg for 4 weeks) significantly reversed haloperidol-induced VCM and tongue protrusions. Biochemical analysis revealed that chronic haloperidol treatment significantly induced lipid peroxidation, decreased glutathione (GSH), superoxide dismutase (SOD), and catalase levels in the brains of rats. Quercetin (25-100 mg/kg for 4 weeks) significantly reduced lipid peroxidation and restored GSH, SOD and catalase levels.


CONCLUSIONS
The results of the present study clearly indicate that quercetin has a protective role against haloperidol-induced orofacial dyskinesia. Consequently, the use of quercetin as a therapeutic agent for the treatment of tardive dyskinesia should be considered.
Naidu
Pattipati S
PS
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160014 Chandigarh, India.
Singh
Amanpreet
A
Kulkarni
Shrinivas K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006220:Haloperidol / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D014150:Antipsychotic Agents; D008315:Malondialdehyde; D011794:Quercetin; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D006220:Haloperidol