doi.org/10.36721/PJPS.2020.33.2.SUP.755-763.1 Pak. J. Pharm. Sci., Vol.33, No.2(Suppl), March 2020, pp.755-763 755 Lauric acid: Its role in behavioral modulation, neuro-inflammatory and oxidative stress markers in haloperidol induced Parkinson’s disease Awais Ali Zaidi 1 , Mahtab Ahmad Khan 1,2* , Zaib Ali Shahreyar 1 and Hammad Ahmed 1 1 Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan 2 Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan Abstract: The study was designed to investigate the neuro-protection of lauric acid (LA) on haloperidol (HPD) induced Parkinson’s disease (PkD) rat model. Rats were divided into group A (normal), group B (diseased, by HPD 1mg/kg i.p. for 14 days), group C (standard treatment, levodopa 30 mg/kg), group D (vehicle coconut oil 1ml/kg), group E (LA 0.66mg/kg) and group F (LA 1.32mg/kg) for 35 days after induction of PkD. The study displayed a state of oxidative stress in the striatum of rat model of PkD as shown from the increased MDA, NO levels and the decreased superoxide dismutase levels. HPD caused an increase in tumor necrosis factor-α level, NF-кB, IL-8 mRNA expression and suppress IL-4 expression. Neuro-protection with LA attenuated the oxidative stress and changes in pro-inflammatory cytokines induced due to PkD induction. The LA treatment also showed improvement in the histo-pathology of the rats’ brain. LA also improved behavioral performances, food intake, weight gain as compared to animal of diseased group and prevented decline in motor activities (assessed Rotarod, and Beam walking test). LA showed significant neuro-protection against oxidative stress, inflammatory cytokines and behavioral changes in HPD induced rat model of PkD. Keywords: Parkinson’s disease, dopamine, substantia nigra, neuro-inflammation, reactive oxygen species. INTRODUCTION PkD is a slowly progressing neuro-degenerative disease, influencing 1%, populace of 65 years, expanding up to 3%, in populace more than 80 years old (Hirtz et al., 2007). PkD is characterized by akinesia, festinating gait, resting tremor, rigidity, postural abnormalities, stooped posture and bradykinesia (Jomova et al., 2010). Clinical indications appear to be just if dopaminergic neural death surpasses a basic limit of 70-80%. In addition, motor and neuro-psychological functions became debilitated due to advancement of disease (Bartus and Johnson Jr, 2017). The standard neuroleptic drug, haloperidol (HPD), for an extended time, used to treat distinctive psychotic diseases. Various patients may develop harmful, incapacitating side effects, including symptoms of PkD like muscle stiffness, depression, bradykinesia and tardive dyskinesia's (Shin and Chung, 2012). HPD showed its effects by blocking the post-synaptic dopamine D 2 receptors in the meso- limbic system caused an increase of dopamine turnover by blockage of the D 2 receptors (Zaidi et al., 2016). Levodopa (LVD) remains the gold standard to treat motor symptoms of PKD. Compared with other presented treatments, LVD is associated with the greatest improvement in motor function (Holloway et al., 2004). Long-term treatment with LVD cause several types of motor fluctuations like dyskinesia, on and off effects, a problem categorized by unpredictable involuntary movements (Group, 2000). The medium chain fatty acid of coconut oil is LA, having 12 carbon back-bone. It is found normally in various trees and animal fats, a noteworthy part of coconut and palm nut oil, which is 45-53%. Metabolic and physiological properties of LA demonstrate a few properties of coconut oil (McCarty and DiNicolantonio, 2016). Coconut oil is rapidly metabolized, readily ingested and LA is well transported and helps scales back the fat collection. LA shows significant antimicrobial action against gram- positive microorganisms and load of parasites and infections as confirmed by various investigations (Mumme and Stonehouse, 2015). The aims of this study were to: Investigate the curative role of LA in HPD induced PkD. To observe changes in behavior (Sensory motor functions), inflammation and oxidative stress. Pharmacological effects of LA on oxidative stress markers (MDA, SOD and NO), mRNA expression of pro- and anti-inflammatory cytokines and behavioral changes in PkD. MATERIALS AND METHODS Animals Total 42 male Wister rats (age 32-40 weeks), weighing (300-325g) obtained from animal research facility at “The University of Lahore” were used for this study, housed under controlled temperature (28°C±2°C) and humidity (60-70%). All animals were kept at 12h dark/light phases. The animals were nourished with water and standard pellet diet ad labium. Study protocol, animal handling was *Corresponding author: e-mail: raomahtab@yahoo.com