fluvoxamine and Parkinsonian-Disorders

Parkinson's disease (PD) is also associated with cognitive impairment and reduced extrinsic supply of dopamine (DA) to the prefrontal cortex (PFC). In the present study, we looked at whether exposure to early life stress reduces DA and serotonin (5-HT) concentration in the PFC thus leading to enhanced cognitive impairment in a Parkinsonian rat model. Maternal separation was the stressor used to develop an animal model for early life stress that has chronic effects on brain and behavior. Sprague-Dawley rats were treated with the antidepressant Fluvoxamine maleate (FM) prior to a unilateral 6-hydroxydopamine (6-OHDA) lesion to model motor deficits in rats. The Morris water maze (MWM) and the forelimb use asymmetry (cylinder) tests were used to assess learning and memory impairment and motor deficits respectively. Blood plasma was used to measure corticosterone concentration and prefrontal tissue was collected for lipid peroxidation, DA, and 5-HT analysis. Our results show that animals exposed to early life stress displayed learning and memory impairment as well as elevated basal plasma corticosterone concentration which were attenuated by treatment with FM. A 6-OHDA lesion effect was evidenced by impairment in the cylinder test as well as decreased DA and 5-HT concentration in the PFC. These effects were attenuated by FM treatment resulting in higher DA concentration in the PFC of treated animals than in non-treated animals. This study suggests that DA and 5-HT signaling in the PFC are responsive to FM and may reduce stress-induced cognitive impairment in PD.

Topics: Animals; Corticosterone; Dopamine; Fluvoxamine; Learning; Learning Disabilities; Lipid Peroxidation; Male; Maternal Deprivation; Memory; Memory Disorders; Neurotransmitter Agents; Nootropic Agents; Oxidopamine; Parkinsonian Disorders; Prefrontal Cortex; Random Allocation; Rats, Sprague-Dawley; Serotonin; Stress, Psychological

Cytokine dysfunction is associated with both depression and Parkinson's disease (PD) pathophysiology. 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-1β, IL-6, TNF-α, TGF-β 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 Fluvoxamine for 30days 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 impairments 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-1β, IL-6 and TNF-α were down-regulated while IL-10 and TGF-β levels 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.

Topics: Age Factors; Animals; Animals, Newborn; Anti-Anxiety Agents; Corpus Striatum; Cytokines; Depression; Desipramine; Disease Models, Animal; Fluvoxamine; Functional Laterality; Lipid Peroxidation; Male; Neurons; Oxidopamine; Parkinsonian Disorders; Psychomotor Performance; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sucrose

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.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antiparkinson Agents; Anxiety; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fluvoxamine; Forelimb; Male; Maternal Deprivation; Maze Learning; Neurotransmitter Agents; Oxidopamine; Parkinsonian Disorders; Pregnancy; Rats; Rats, Sprague-Dawley