Reversal of reserpine-induced orofacial dyskinesia and cognitive dysfunction by quercetin.
Tardive dyskinesia (TD) is a serious neurological syndrome associated with long-term administration of neuroleptics to humans and experimental animals. The pathophysiology of this disabling and commonly irreversible movement disorder is still obscure. It may be caused by a loss of dopaminergic cells or may be due to free radicals as a product of high synaptic dopamine levels. Quercetin is a bioflavonoid with strong antioxidant properties. Repeated treatment with reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats. Chronic treatment with quercetin for a period of 4 weeks to reserpine-treated animals significantly and dose dependently (50 and 100 mg/kg) reduced the reserpine-induced VCMs and TPs. Reserpine-treated animals also showed poor retention of memory in elevated plus-maze task paradigm. Chronic quercetin administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that chronic reserpine treatment significantly induced lipid peroxidation and decreased the glutathione (GSH) levels in the brains of rats. Chronic reserpine-treated rats showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD) and catalase. Chronic administration of quercetin dose dependently (50-100 mg/kg) and significantly reduced the lipid peroxidation and restored the decreased GSH levels by chronic reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The results of the present study clearly indicated that quercetin has a protective role against reserpine-induced orofacial dyskinesia and memory impairment. Consequently, the use of quercetin as a therapeutic agent for the treatment of TD should be considered.
Naidu
Pattipati S
PS
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Singh
Amanpreet
A
Kulkarni
Shrinivas K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002374:Catalase / Q000097:blood / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005978:Glutathione / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000097:blood; D014163:Transfer, Psychology / Q000187:drug effects
D014150:Antipsychotic Agents; D001798:Blood Proteins; D008315:Malondialdehyde; D012110:Reserpine; D011794:Quercetin; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione