Fluoxetine reduces anxiety-like behavior but increases motor impairments in the early stages of a progressive model of Parkinson's disease.
Source: PubMed, NCBI / U.S. National Library of Medicine
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized not only by the gradual loss of motor control but also by a wide range of non-motor symptoms, including anxiety and depression, which can precede motor dysfunction by years. These psychiatric manifestations are commonly managed with selective serotonin reuptake inhibitors (SSRI). However, their impact on motor function in the early stages of PD remains controversial. In this study, we investigated the effects of fluoxetine in a progressive model of parkinsonism induced by repeated low-dose reserpine in male Wistar rats. Animals received short- (four injections) or middle-term (ten injections) reserpine (0.1 mg/kg, one every 48 h) treatment combined or not with daily fluoxetine (10 mg/kg) administration, and were evaluated for catalepsy, oral movements, open field behavior, body weight, and immunoreactivity for tyrosine hydroxylase (TH) and serotonin (5-HT). Fluoxetine decreased anxiety-like behavior, assessed by reducing the time animals spend exploring the center of the apparatus; potentiated reserpine-induced motor deficits, leading to earlier onset of cataleptic immobility, enhanced oral dyskinesia, reduced exploratory activity and body weight loss. In addition, fluoxetine alone decreased TH immunoreactivity in the dorsal striatum while increasing 5-HT labeling in the dorsal raphe nucleus, suggesting serotonergic modulation of dopaminergic circuits. In conclusion, fluoxetine a
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized not only by the gradual loss of motor control but also by a wide range of non-motor symptoms, including anxiety and depression, which can precede motor dysfunction by years. These psychiatric manifestations are commonly managed with selective serotonin reuptake inhibitors (SSRI). However, their impact on motor function in the early stages of PD remains controversial. In this study, we investigated the effects of fluoxetine in a progressive model of parkinsonism induced by repeated low-dose reserpine in male Wistar rats. Animals received short- (four injections) or middle-term (ten injections) reserpine (0.1 mg/kg, one every 48 h) treatment combined or not with daily fluoxetine (10 mg/kg) administration, and were evaluated for catalepsy, oral movements, open field behavior, body weight, and immunoreactivity for tyrosine hydroxylase (TH) and serotonin (5-HT). Fluoxetine decreased anxiety-like behavior, assessed by reducing the time animals spend exploring the center of the apparatus; potentiated reserpine-induced motor deficits, leading to earlier onset of cataleptic immobility, enhanced oral dyskinesia, reduced exploratory activity and body weight loss. In addition, fluoxetine alone decreased TH immunoreactivity in the dorsal striatum while increasing 5-HT labeling in the dorsal raphe nucleus, suggesting serotonergic modulation of dopaminergic circuits. In conclusion, fluoxetine administration prevented anxiety-like behavior but anticipated and exacerbated the motor changes caused by reserpine. Furthermore, simultaneous treatment with fluoxetine and reserpine worsened motor and behavioral impairments irrespective of TH changes, indicating that functional disturbances may precede dopaminergic degeneration. These findings highlight that fluoxetine, while targeting mood alterations, may exacerbate motor alterations during prodromal and initial stages of parkinsonism.