Co-administration of nitric oxide (NO) donors prevents haloperidol-induced orofacial dyskinesia, oxidative damage and change in striatal dopamine levels.
Tardive dyskinesia (TD) has been considered as a major clinical issue in the treatment of schizophrenia. Various animal studies have indicated the role of oxidative stress and nitric oxide pathway in haloperidol-induced TD. The present study investigated the effect of NO donors (molsidomine and l-arginine) in haloperidol-induced TD in rats. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCMs), tongue protrusions, and facial jerking in rats which was dose dependently inhibited by NO donors. Besides, haloperidol also increased striatal superoxide anion levels and decreased striatal NO and citrulline levels which were prevented by molsidomine and l-arginine. On chronic administration of haloperidol, there was a decrease in the striatal levels of dopamine, which was again reversed by treatment with NO donors. The findings of the present study suggested for the involvement of NO in the development of neuroleptic-induced TD and indicated the potential of NO donors as a possible therapeutic option. Furthermore, a sub-study on a possible schizophrenic phenotype, i.e. a possible clinical worsening in the animals receiving NO donors and neuroleptics will substantiate the clinical utility of the study.
Bishnoi
Mahendra
M
Centre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University, Chandigarh, 160014, India.
Chopra
Kanwaljit
K
Kulkarni
Shrinivas K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001120:Arginine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000517:prevention & control*; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D009069:Movement Disorders / Q000517:prevention & control; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D014150:Antipsychotic Agents; D020030:Nitric Oxide Donors; D013481:Superoxides; D002956:Citrulline; D001120:Arginine; D008981:Molsidomine; D006220:Haloperidol; D004298:Dopamine