No effect of C1473G polymorphism in the tryptophan hydroxylase 2 gene on the response of the brain serotonin system to chronic fluoxetine treatment in mice

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

“…Now we found that prolonged treatment with fluoxetine decreased 5-HT and 5-HIAA levels in the brain of zebrafish. This finding agrees with those observed in mice chronically treated with fluoxetine [ 16 , 17 ] and seems to result from a disruption of the mechanism of 5-HT reutilization in the brain [ 25 ]. However, in mice this fluoxetine-induced decrease in the 5-HT level is observed after 30 [ 16 ] or 60 [ 17 ] days of treatment, while in zebrafish 3-day-long treatment is sufficient to dramatically reduce the 5-HT level.…”

“…This finding agrees with those observed in mice chronically treated with fluoxetine [ 16 , 17 ] and seems to result from a disruption of the mechanism of 5-HT reutilization in the brain [ 25 ]. However, in mice this fluoxetine-induced decrease in the 5-HT level is observed after 30 [ 16 ] or 60 [ 17 ] days of treatment, while in zebrafish 3-day-long treatment is sufficient to dramatically reduce the 5-HT level. It seems that the persistent treatment during 72 h by fluoxetine dissolved in aquarium water accelerates the fluoxetine-induced drop of 5-HT level in the zebrafish brain.…”

“…According to the neurotrophic hypothesis, the therapeutic effect of SSRIs is mediated by activation of cAMP-response protein (CREB) and synthesis of the brain derived neurotrophic factor (BDNF) [ 13 , 14 ]. At the same time, prolonged SSRI treatment affects the brain’s 5-HT homeostasis, including its synthesis, release, reception, reuptake, and oxidation [ 15 ], as well as decreases the 5-HT level in mouse brains [ 16 , 17 ].…”

Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure

“…These studies indicate a link between disrupted 5-HT levels and social dominance, alternation rates, and tactile sensitivity. Acute FLX treatment has been shown to increase extracellular 5-HT levels ( Malagié et al, 1995 ), while chronic treatment (lasting at least three weeks) may actually reduce 5-HT levels through autoreceptor feedback and reduced transporter-mediated 5-HT recycling ( Siesser et al, 2013 ; Bazhenova et al, 2017 ). However, the literature on this is inconsistent ( Jacobsen et al, 2016 ).…”

“…Within 30 min of exposure FLX increases extracellular 5-HT, dose-dependently, within the frontal cortex, hippocampus, and raphe ( Malagié et al, 1995 ). Cortical and striatal 5-HT tissue levels are depleted with chronic (three weeks) exposure ( Siesser et al, 2013 ; Bazhenova et al, 2017 ), but extracellular 5-HT levels seem to remain elevated ( Jacobsen et al, 2016 ). Our data suggest the maternal FLX exposure altered the circuits mediating this social hierarchy behavior in a complex manner such that they no longer respond to 5-HT in a typical way.…”