Possible beneficial effect of peroxisome proliferator-activated receptor (PPAR)--α and γ agonist against a rat model of oral dyskinesia.
Tardive dyskinesia is a type of hyperkinetic movement disorder which consists of abnormal involuntary movements, characterized by orofacial movements. Previous studies suggest that oxidative stress and neuro-inflammation play important role in the pathogenesis of TD. Recently, PPAR-α and PPAR-ϒ have been reported as neuroprotective agent in various animal models. The present study investigated the neuroprotective effect of PPAR-ϒ agonist, pioglitazone (20 and 40 mg/kg, p.o.) and PPAR-α agonist, fenofibrate (100 and 200mg/kg, p.o.) in an animal model of oral dyskinesia. Oral dyskinesia was induced by chronic administration of haloperidol (1 mg/kg i.p.) for 21 days. Chronic administration of haloperidol significantly increased vacuous chewing movements, tongue protrusions, facial jerking, sniffing and grooming in rats which was dose-dependently inhibited by pioglitazone and fenofibrate. Further, it also decreased % retention of memory in an elevated plus maze test on day 22. Chronic administration of haloperidol also induced oxidative damage and neuroinflammation (TNF-α and IL-1β) in brain regions. The fenofibrate and pioglitazone were able to reverse the behavioral and biochemical changes induced by haloperidol. Further the study proposed the antioxidant and antiinflammatory effects of both PPAR agonists in this model. We concluded that administration of pioglitazone and fenofibrate individually or in combination along with antipsychotic in the treatment of schizophrenia, prevent or delay the symptoms of oral dyskinesia.
Department of Pharmacology, I.S.F. College of Pharmacy, Moga 142001, Punjab, India.
Sania
S
Grover
Puneet
P
Kumar
Kuldeep
K
Singh
Vir
V
Vikram
R D
RD
Budhiraja
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D006220:Haloperidol / Q000009:adverse effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009055:Mouth / Q000503:physiopathology*; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology; D018384:Oxidative Stress; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology
D014150:Antipsychotic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D007770:L-Lactate Dehydrogenase; D006220:Haloperidol; D011345:Fenofibrate; D000077205:Pioglitazone
Choriform; Fenofibrate; Haloperidol; Oral dyskinesia; Pioglitazone; Vacuous chewing movements