Research Article RESVERATROL REVERSES THE RESTRAINT STRESS-INDUCED COGNITIVE DYSFUNCTION INVOLVING BRAIN ANTIOXIDANT SYSTEM IN RATS ASHWIN R RAI, SAMPATH MADHYASTHA * , LATHA V PRABHU, VASUDHA V SARALAYA, SUDHANSHU SEKHAR SAHU Department of Anatomy, Kasturba Medical College, Mangalore, Manipal University, Karnataka, India 575004. Email:sampath.m@manipal.edu Received: 21 Nov 2013, Revised and Accepted: 28 Dec 2013 ABSTRACT Objective:Restraint stress in rats is known to adversely affect the behavior especially memory dysfunctions in rats. Though there are many factors involved in this stress-induced memory impairment, damage to the antioxidant system in the brain is also known to be a causative factor. Resveratrol is known to exert its neuroprotective potentials by up regulating several antioxidant systems. Hence, the present study was undertaken to evaluate the neuroprotective effect of resveratrol against stress-induced cognitive impairment and involvement of brain antioxidant enzymes. Methods: Male rats were subjected to restraint stress for 6 hours consecutively for 21 days. Another sets of rats received similar intensity and duration of stress along with either 10 or 20mg/kg dose of resveratrol for 28 days with its administration before a weak of stressing procedure. A control group of rats was also served in the experiment. The behavioural studies include active avoidance and open field tests. Thereafter the rats were sacrificed and the whole brain homogenate was subjected to lipid peroxidation and total antioxidants (TAO)estimation. Results: Restraint stress has impaired motor activity, learning and memory activities and resveratrol treatment has reversed this cognitive dysfunction. Restraint stress caused an alteration in oxidative stress markers with a significant increase in lipid peroxidation and depletion of total antioxidant activities, which was reversed by resveratrol. Conclusion: Results of the present study confirm that resveratrol can reverse the stress induced memory dysfunction by exerting its antioxidant potentials. Keywords: Lipid peroxidation, Memory impairment, Restraint stress,Resveratrol, Total antioxidants. INTRODUCTION Stress induced neurotoxic effects are largely mediated by hypothalamic-pituitary-adrenocortical (HPA) axis with an increased brain corticosterone level[1] which intern affects expression of neurotransmitters, synaptic proteins and also affects the brain antioxidant defense system [2,3]. Stress induced neuronal damage associated with behavioral changes especially cognitive dysfunction is well reported [4,5]. The brain and nervous system are prone to oxidative stress, and are inadequately equipped with antioxidant defense systems to prevent ‘ongoing’ oxidative damage. Indeed, increased oxidative damage, mitochondrial dysfunction [6], accumulation of oxidized aggregated proteins is known to kill neurons. Restraint stress causes robust increase in the production of reactive oxygen species and consequent oxidative damage, with a concomitant decline in in vivo antioxidant defenses contributing to the pathology of stress-induced neurotoxic effects. Stress can alter cellular homeostasis by oxidative damage in brain which in turn involves behavioral, biochemical and morphological changes. Restraint stress in mice has been shown to cause neuronal death in the cerebral cortex which was prevented by antioxidant pretreatment with an associated decrease in reactive oxygen species population [7]. Antioxidants which effectively enter the nervous system, act as antioxidants themselves and are well absorbed from the GI tract would be ideal candidates for protection of the brain and nervous system from oxidative damage.Hence in the present study the antioxidant potential of resveratrol was evaluated. Resveratrol is a phytoalexin produced by several plants that is sold as a nutritional supplement. It has also been produced by chemical synthesis [8]. A number of beneficial health effects, such as anti- cancer, antiviral, neuroprotective, anti-aging, anti-inflammatory and life-prolonging effects have been reported in non-human species (e.g. rats).Resveratrol was reported effective against neuronal cell dysfunction and cell death, and this theory could help against diseases such as Huntington's disease [9] and Alzheimer's disease [10]. In addition resveratrol decreased anxiety and increased cortex/hippocampus dependent memory of animals subjected to blunt head trauma [11]. Resveratrol is able to cross the blood brain barrier and exerts potent antioxidant features [12]. With many supportive results we tested the neuroprotective effect of resveratrol against stress induced memory dysfunction. MATERIALS AND METHODS Animals Four months old male Wistar rats (weighing 220g±20) bred in- house was used in the present study. Animals were maintained under controlled conditions of light (10h- light: 14h- dark), temperature (22±3°C), and humidity (approximately 50±10%). All rats were maintained on the standard rat food and water ad libitum. For housing the rats’ plastic cages with paddy husk as bedding material was used. The institutional animal ethical committee has approved this research protocol. Stressing procedure Rats were assigned to a daily restraint stress for 21 days in a wire mesh restrainer for 6 hours [13]. The wire mesh restrainer had a wooden base and stainless steel wire mesh restrainer hinged to the base. The restrainer with dimensions of 11cm (L) x 8cm (B) x 8cm (H) was used to stress. This type of restrainer will only restrict the movements of the animal without causing any pain, discomfort or suffocation. Animal groups (n=6) Group 1: Control and received sodium carboxymethylcellulose as vehicle Group 2: Received 21 days restraint stress (6h daily) Group 3: Received 21 days stress + resveratrol (10mg/kg body weight dose) for 28 days (Resveratrol was given a week prior to stress treatment) Group 4: Received 21 days stress + resveratrol (20mg/kg body weight dose) for 28 days (Resveratrol was given a week prior to stress treatment) International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 6, Issue 1, 2014 Academic Sciences