Neuroscience
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Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (n=9) or mixed with citalopram 5 mg/kg/day (n=27). ⋯ As was observed with citalopram, fluoxetine induced significant reductions of TPH cell counts in the DRN (39%), MRN (38%) and RMN (41%), with no significant differences in the CLN. These results indicate that SERT inhibition can alter the regulation of TPH, the rate limiting enzyme for serotonin biosynthesis. This persistent and regionally specific downregulation of serotonin biosynthesis may account for some of the clinical withdrawal symptoms associated with drugs that inhibit SERT.