Anti‐parkinsonian effects of fluvoxamine maleate in maternally separated rats

Abstract

Exposure to early life stress has been shown to result in anxiety-like symptoms and exacerbates degeneration of dopaminergic neurons in a rat model of Parkinson's disease (PD). First line treatment for anxiety disorders includes the use of Fluvoxamine maleate (FM). In this study, we investigated whether treating anxiety-like symptoms with FM has an effect in alleviating the neurotoxic effects of 6-OHDA in a parkinsonian rat model. Early maternal separation was used to create a rat model that depicts anxiety-like symptoms. Maternally separated adult Sprague-Dawley rats were treated with FM prior to and following lesion with 6-hydroxydopamine (6-OHDA). The elevated plus-maze (EPM) and the forelimb akinesia tests were used to evaluate anxiety-like symptoms and motor impairment respectively. Blood plasma was used to measure corticosterone concentration, and striatal tissue was collected for dopamine (DA) and serotonin (5-HT) analysis. Our results show that animals exposed to early life stress displayed increased anxiety-like symptoms and elevated basal plasma corticosterone concentration which were attenuated by treatment with FM. A 6-OHDA lesion effect was evidenced by impairment in the forelimb akinesia test as well as decreased DA and 5-HT concentrations in the lesioned striatum. These effects were attenuated on DA neurons by FM treatment in the pre-lesion treated as opposed to the post-lesion treated rats. This study suggests that early treatment of anxiety-like behavior decreases the vulnerability of DA neurons to neurotoxic insults later in life thus slowing down DA degeneration in PD.

Long-Term Treatment with Fluvoxamine Decreases Nonmotor Symptoms and Dopamine Depletion in a Postnatal Stress Rat Model of Parkinson’s Disease

“…This study is aimed at assessing the long-term effects of Fluvoxamine in managing anxiety/depressive-like symptoms and cognitive deficits and reducing motor dysfunctions in a parkinsonian rat model. Our objective was to evaluate the Plasma corticosterone levels were measured to confirm the effectiveness of the stress protocol in dysregulating the HPA axis resulting in anxiety/depressive symptoms and cognitive deficits [27,30,36,37,56]. We found that maternally separated (MS) rats had higher corticosterone levels when compared to nonseparated (NS) rats in agreement with a study by Daniels et al [27] who showed that stress elevates blood corticosterone levels.…”

“…A total of 40 male Sprague-Dawley (SD) rats, weighing between 6 g at postnatal day (PND) 1 and 300 g at PND 76, was used. Pregnant SD rats were obtained from the Biomedical Resource Unit of the University of KwaZulu-Natal and were housed in polypropylene cages (38 × 32 × 16 cm) under controlled temperature (21 ± 2°C) and humidity (55-60%) until they gave birth [30]. At birth, pups were crossfostered and randomly divided into 4 groups as follows: (1) nonmaternally separated (NS), (2) nonmaternally separated treated with Fluvoxamine (NSF), (3) maternally separated (MS), and (4) maternally separated treated with Fluvoxamine (MSF) (n = 10/group).…”

“…In PD, it is well documented that motor dysfunctions may result from dopamine (DA) depletion in the striatum, the prefrontal cortex, and the hippocampus [19,30,45,88,89]. This study only focused on how Fluvoxamine was indirectly implicated in the dopaminergic neuronal integrity in our PD model [90,91].…”

Effects of early life stress on biochemical indicators of the dopaminergic system: a 3 level meta-analysis of rodent studies

“…The publications included in the analysis were:(Adrover et al 2007; Alonso, Navarro, and Rodriguez 1994; Baharnoori, Bhardwaj, and Srivastava 2013; Baier et al 2014; Bakos et al 2004; Basta-Kaim et al 2011; Berger et al 2002; Bingham et al 2013; Bitanihirwe et al 2010; Brenhouse, Lukkes, and Andersen 2013; Cabib, Puglisi-Allegra, and D’Amato 1993; Cai et al 2013; Camp, Robinson, and Becker 1984; Carboni et al 2010; Chocyk et al 2011; Kwok Ho Christopher, Choy, De Visser, and Van Den Buuse 2009; K. H C Choy and van den Buuse 2008; Cory-Slechta et al 2009; Cory-slechta et al 2013; Dallé, Daniels, and Mabandla 2016; Delattre et al 2016; L. W. Fan et al 2011; L.-W.…”

Inbuilt novel bioretardant feature of biopolymer isolated from cucumis sativa for designing drug loaded bionanosuspension

“…Electro-convulsive therapy, Psychotherapies and Cognitive behavior therapy are particularly effective for the most severe and resistant depressions 1 . Fluvoxamine is one of the antidepressants commonly used as first line treatment for major depressive disorders 2,3 SSRIs (selective serotonin reuptake inhibitor) are antidepressant drugs that increase serotoninergic neurotransmission via the selective inhibition of neuronal reuptake of serotonin 4,5 . Fluvoxamine is BCS class II drug which having low solubility and high permeability but it is practically soluble in ethanol, so it is suitable for formulating nanosuspension.…”