Reversal of Reserpine-Induced Orofacial Dyskinesia and Cognitive Dysfunction by Quercetin

Abstract

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.

Some aspects of thein vivo neuroprotective capacity of flavonoids: Bioavailability and structure-activity relationship

“…In this sense, the chronic quercetin treatment for 30 days in doses of 10, 25 and 50 mg/kg, reverses cognitive deficits in aged and ethanol-intoxicated mice . Quercetin in doses of 50 and 100 mg/kg significantly and dose-dependently reduced the reserpine-induced vacuous chewing movements and tongue protrusions in rats (Naidu et al, 2004). Besides, this flavonoid in doses of 25-100 mg/kg proved to be a useful agent in neuroleptic-induced orofacial dyskinesia .…”

“…Reports on the neuroprotective effects of quercetin have also utilized chronic administration for some weeks and by an oral route. Hence, quercetin treatment for 30 days reverses cognitive deficits in aged and ethanol-intoxicated mice , and quercetin for a period of 4 weeks significantly and dose-dependently reduced reserpineinduced vacuous chewing movements and tongue protrusions in reserpine-treated animals (Naidu et al, 2004). After 21 days quercetin also proved to be a useful therapeutic agent in neuroleptic-induced orofacial dyskinesia .…”

Effect of aronia melanocarpa fruit juice on reserpine-induced hypokinesia and oxydative stress in rats

“…Dopamine VMAT blockade by reserpine promotes dopamine oxidative catabolism by MAO (9). As a result, dopamine-quinones and hydrogen peroxide are formed leading to oxidative stress (4,17) in areas of the brain rich in monoamines such as the basal ganglia which are more vulnerable to free radical damage (15). The neuronal damage of the basal ganglia is associated with damage of voluntary movements (7).…”

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice

“…The neuro-protective effects of plants containing polyphenolic compounds such as quercetin [43] and anthocyanins [44] have been previously reported. Moreover, it has been demonstrated that polyphenolic compounds have Ache inhibitory activity and antioxidant effect on brain [38, 45, 46].…”