The effects of fluvoxamine maleate in a post-natal stress model of neurodegeneration

Abstract

Parkinson’s disease (PD) is the most common movement disorder characterized by loss of dopamine neurons in the substantia nigra. Treatment strategies focus mainly on retarding the progression of the disease since the serological evaluation of new treatments is difficult. Motor symptoms of PD appear late as opposed to non-motor symptoms (i.e. depression, anxiety) frequently preceding motor symptoms. Fluvoxamine maleate (FM) is an antidepressant widely used to treat depression and anxiety disorders. In patients with both depression and Parkinsonism, treatment with FM may delay motor symptoms and protect dopamine neurons. We aimed to use an animal model of depression to investigate the neuroprotective effects of FM on a postnatal stressed model of neurodegeneration. The ethics clearance was 061/14/Animal.Sprague-Dawley rats (N = 80) were divided into eight groups. Maternal separation was used to create an animal model of depression. Behavioural tests (open field, elevated plus-maze, step and cylinder test) were conducted prior and after the injection of 6-OHDA into the medial forebrain bundle to mimic Parkinsonism. Animals received FM (25 mg/kg, i.p/day) pre and post-lesion and were sacrificed on postnatal day 76. Blood and brain tissues were collected for corticosterone, lipid peroxidation, dopamine and serotonin analyses.Maternal separation caused depressive-like symptoms prior to the 6-OHDA lesion and motor impairment after the lesion. Plasma corticosterone levels and lipid peroxidation were increased in the striatum and the prefrontal cortex while dopamine and serotonin levels decreased. Treatment with FM reversed these effects in maternally separated animals and showed neuroprotection to dopamine neurons in our parkinsonian rat model. Parkinson’s disease (PD) is the most common movement disorder characterized by loss of dopamine neurons in the substantia nigra. Treatment strategies focus mainly on retarding the progression of the disease since the serological evaluation of new treatments is difficult. Motor symptoms of PD appear late as opposed to non-motor symptoms (i.e. depression, anxiety) frequently preceding motor symptoms. Fluvoxamine maleate (FM) is an antidepressant widely used to treat depression and anxiety disorders. In patients with both depression and Parkinsonism, treatment with FM may delay motor symptoms and protect dopamine neurons. We aimed to use an animal model of depression to investigate the neuroprotective effects of FM on a postnatal stressed model of neurodegeneration. The ethics clearance was 061/14/Animal. Sprague-Dawley rats (N = 80) were divided into eight groups. Maternal separation was used to create an animal model of depression. Behavioural tests (open field, elevated plus-maze, step and cylinder test) were conducted prior and after the injection of 6-OHDA into the medial forebrain bundle to mimic Parkinsonism. Animals received FM (25 mg/kg, i.p/day) pre and post-lesion and were sacrificed on postnatal day 76. Blood and brain tissues were collected for corticosterone, lipid peroxidation, dopamine and serotonin analyses. Maternal separation caused depressive-like symptoms prior to the 6-OHDA lesion and motor impairment after the lesion. Plasma corticosterone levels and lipid peroxidation were increased in the striatum and the prefrontal cortex while dopamine and serotonin levels decreased. Treatment with FM reversed these effects in maternally separated animals and showed neuroprotection to dopamine neurons in our parkinsonian rat model.