Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction
Copyright policy )Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction
Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5-HTT) blockade during adulthood but not during development impairs basal ganglia-dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia-dependent behavior is indicated by the reversal of behavioral deficits throughl-DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRI-based therapy.
- King’s University United States
- Columbia University United States
Male, Movement Disorders, Dose-Response Relationship, Drug, Dopamine, Dopamine Agents, Age Factors, Cell Count, Homovanillic Acid, Mice, Transgenic, Basal Ganglia, Drug Administration Schedule, Levodopa, Mice, Animals, Newborn, Fluoxetine, Exploratory Behavior, 3,4-Dihydroxyphenylacetic Acid, Animals, Drug Interactions, Chromatography, High Pressure Liquid
Male, Movement Disorders, Dose-Response Relationship, Drug, Dopamine, Dopamine Agents, Age Factors, Cell Count, Homovanillic Acid, Mice, Transgenic, Basal Ganglia, Drug Administration Schedule, Levodopa, Mice, Animals, Newborn, Fluoxetine, Exploratory Behavior, 3,4-Dihydroxyphenylacetic Acid, Animals, Drug Interactions, Chromatography, High Pressure Liquid
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