American Journal of Pharmacological Sciences, 2015, Vol. 3, No. 3, 74-78 Available online at http://pubs.sciepub.com/ajps/3/3/4 © Science and Education Publishing DOI:10.12691/ajps-3-3-4 Antidepressant Effect of Diclofenac against Experimental Parkinson’s Rat Model Sadaf Naeem 1,* , Rahila Najam 1 , Nousheen Alam 2 1 Department of pharmacology, University of Karachi, Pakistan 2 Department of pharmacology, Federal Urdu University of Karachi, Pakistan *Corresponding author: ssadafnaeem@gmail.com Received May 31, 2015; Revised June 17, 2015; Accepted July 05, 2015 Abstract Previous clinical studies confirm the presence of inflammatory mediators like tissue necrotic factor alpha (TNF-α) and interleukins-1β in depressive patients are the main cause of depression and the use of non- steroidal anti-inflammatory drugs (NSAIDs) especially cyclo-oxygenase-2 (COX-2) inhibitors are associated with a marked reduction in the symptoms of depression. In our study we investigated the role of diclofenac in ameliorating depression in chlorpromazine (CPZ) induced PD model. Forty Wistar albino rats were divided equally into 4 groups, Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II, III and IV were treated with chlorpromazine (3mg/kg/day ) via the intraperitoneal route once a day for 21 days. Diclofenac (20mg/kg/day) was given orally to group III and standard drug L-dopa/carbidopa (30mg/kg/day) orally was given to group IV for 21 days. Group II was negative control, and all treated group received 3mg/kg/day i.p CPZ for 21 days. CPZ was administered 30 min before the administration of test drugs, antidepressant effects of diclofenac were examined by using open field activity, cage crossing and forced swimming test. In the open field, diclofenac and standard drug (L-dopa/carbidopa) animals showed significant (P<0.001) improved number of square crossed in 10 minutes, increased grooming period and relatively more time spent in center of open field arena after 10 and 21 days as compared to CPZ group. In cage crossing diclofenac showed highly significant (P<0.001) improved activity of cage crossing after 21 days just similar to standard group (L-dopa/carbidopa), while CPZ significantly showed immobility and depressive behavior. In FST diclofenac was able to restore significantly the immobility time and decrease swimming effort as well as climbing duration induced by CPZ. Taken together, the present work evidenced antidepressant effects of diclofeanc. This may be through inhibiting depressive markers like TNF-α and IL-1β in brain compartments, and possibly nor-adrenergic mechanism could also play a role. Keywords: non steroidal anti-inflammatory drugs, diclofenac, depression, TNF-α, IL-1β, chlorpromazine, FST Cite This Article: Sadaf Naeem, Rahila Najam, and Nousheen Alam, “Antidepressant Effect of Diclofenac against Experimental Parkinson’s Rat Model.” American Journal of Pharmacological Sciences, vol. 3, no. 3 (2015): 74-78. doi: 10.12691/ajps-3-3-4. 1. Introduction Mood variations for example, dementia and depression are cardinal non motor symptoms of Parkinson's disease, just as tremors and rigidity, these non motor symptoms affects patients quality of life and burden to care giver. Depression and cognitive impairment is correlated and often present at the point when confronting a diagnosis of Parkinson's disease. Chronic neuroinflammation have been associated with the etiopathogenesis of different neurological problems especially parkinsons disease and may affects the complex brain functions like sleep, memory and depression [19]. In inflammatory condition brain resident cells like microglia releases number of inflammatory mediators including prostaglandins (PGs), interleukins (IL), TNF-alpha and other cytokines. In recent studies TNFα, IL-1β, IL-6 and C-reactive proteins were found elevated in parkinson disease associated depressive patients which indicates that inflammation is the major cause of depression [7]. These proinflammatory cytokines hypothalamus-pituitary-adrenal axis and sympathetic nervous system become activated and upregulate the levels of glucocorticoid and catecholamines [9]. Neurotransmitters such as serotonin and dopamine modify vital behaviors, especially learning and memory, eating patterns, mood variations, sleep and locomotion [10,11]. Depression is related to the levels of monoamines in the brain. Proinflammatory cytokines can affect monoamines regulation and uptake; thereby activate adrenal corticotrophin hormone and cortisol. The over expression of cortisol is the key link between the chronic stress and depression [3]. Regardless of advances in the treatment of parkinson's disease, there is a need for neuroprotection, treatment of motor and non motor symptoms, and treatment of Inflammation. NSAIDs readily cross blood brain barriers and inhibits microgial released cyclo-oxygenases and other cytokines. Recently Al-Amin et al [1] investigated that diclofenac along with sertraline significantly inhibit inflammatory