Marzyeh Kamyar - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Bibi Marjan Razavi - Targeted Drug Delivery Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Faezeh Vahdati Hasani - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Soghra Mehri - Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Amir Foroutanfar - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Hossein Hosseinzadeh - Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s):Long-term treatment with antipsychotics causes serious side effects such as tardive dyskinesia that characterized by abnormal movements in the orofacial region. Oxidative stress in the brain specific area is implicated in the pathophysiology of tardive dyskinesia. In this study the protective effect of crocin on haloperidol-induced orofacial dyskinesia was evaluated. Materials and Methods:Haloperidol (۱ mg/kg, IP) and crocin (۱۰, ۲۰ and ۴۰ mg/kg, IP) were administrated to rats for ۲۱ days. Behavioral assessments such as orofacial dyskinesia movements, open field test and elevated plus maze (EPM) were evaluated every week. Malondealdehyde (MDA) and glutathione (GSH) levels in the hippocampus, cortex and striatum were also measured. Results: Haloperidol increased vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats and co-administration of crocin (۲۰ and ۴۰ mg/kg) significantly reduced them. Furthermore, haloperidol decreased the locomotor and exploratory activities (rearing) in the open field test and decreased the percentage of entries into open arms and the percentage of the time spent on open arms in the EPM. Pretreatment with crocin (۱۰ mg/kg) modified haloperidol effects on these behavioral parameters. Haloperidol induced lipid peroxidation in three brain regions, whereas crocin co-administration reduced the MDA and restored the decreased GSH levels. Conclusion: Our finding suggests that oxidative stress has an important role in the development of tardive dyskinesia. Crocin showed protective effect against haloperidol induced tardive dyskinesia and as a potent naturally antioxidant could be a new and useful drug and a possible therapeutic option for the treatment of tardive dyskinesia.

Crocin, Haloperidol, Lipid Peroxidation, Orofacial dyskinesia, Oxidative stress