Behavioural Brain Research 316 (2017) 189–196 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Fluvoxamine maleate normalizes striatal neuronal inflammatory cytokine activity in a Parkinsonian rat model associated with depression Ernest Dallé, Willie M.U. Daniels, Musa V. Mabandla ∗ School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa h i g h l i g h t s • Early maternal separation caused anhedonia and exacerbated the effects of 6-OHDA in lesioned rats. • Fluvoxamine reversed the effects of 6-OHDA lesion by modulating cytokine gene expression in the striatum of treated rats. • Fluvoxamine normalized pro- and anti-inflammatory cytokine expression in the striatum of treated rat. a r t i c l e i n f o Article history: Received 8 June 2016 Received in revised form 1 August 2016 Accepted 3 August 2016 Available online 25 August 2016 Keywords: Fluvoxamine maleate Depression Inflammatory cytokines Striatum Parkinson’s disease a b s t r a c t Cytokine dysfunction is associated with both depression and Parkinson’s disease (PD) pathophysiol- ogy. Inflammatory cytokines in neural and behavioral processes are involved in the production and/or maintenance of depression in PD. In this study we looked at how Fluvoxamine treatment regulates depressive-like signs, motor impairments and the expression of IL-1, IL-6, TNF-, TGF- and IL-10 cytokines in the striatum of a stressed Parkinsonian rat model. Early maternal separation was used to model stress and depressive-like signs in rats. Maternally separated adult rats were treated with Flu- voxamine for 30 days prior to 6-hydroxydopamine (6-OHDA) lesion. The sucrose preference test (SPT) and the limb-use asymmetry test (cylinder test) were used to evaluate anhedonia and motor impair- ments respectively. Lipid peroxidation and cytokine expression were measured in striatal tissue using ELISA and real-time PCR techniques respectively. Our results show that maternal separation resulted in anhedonia and exacerbated 6-OHDA lesion but Fluvoxamine treatment attenuated these effects. Lipid peroxidation, mRNA levels of IL-1, IL-6 and TNF- were down-regulated while IL-10 and TGF- lev- els were up-regulated in the lesioned striatum of Fluvoxamine treated rats. This study shows that early treatment with Fluvoxamine may attenuate inflammation on injured striatal neurons by favoring anti- inflammatory cytokine expression while decreasing pro-inflammatory cytokine release in the brain. This suggests a role of Fluvoxamine as a potential therapeutic intervention targeting neuronal inflammation associated with PD. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Early exposure to emotional stress such as maternal separation has been shown to cause long-term neurochemical and behav- ioral changes later in life [1]. These changes include depression, a psychiatric disorder commonly encountered non-motor fea- tures of Parkinson’s disease (PD) [2]. The estimated prevalence of depression in PD is between 40–50% in all PD cases [3]. This high ∗ Corresponding author. E-mail addresses: mabandlam@ukzn.ac.za, 212561283@stu.ukzn.ac.za (M.V. Mabandla). prevalence of depression in PD has prompted the idea that degen- erated nigrostriatal system may play a key role in depression [4]. The pathophysiology of PD also includes the presence of -synuclein-containing aggregates in the substantia nigra pars compacta (SNpc) which may suggest the activation of glial cells and dysfunction in pro and/or anti-inflammatory factor levels com- mon in PD associated with depression [5,6]. For instance, the chronic release of pro-inflammatory cytokines by activated astro- cytes and microglia (the resident innate immune cells) leads to the exacerbation of DA neuron degeneration in the SNpc [6,7]. Anti- inflammatory cytokines may also inhibit microglial activation by reducing reactive oxygen species which can be evaluated via lipid http://dx.doi.org/10.1016/j.bbr.2016.08.005 0166-4328/© 2016 Elsevier B.V. All rights reserved.