Chronic fluoxetine administration increases the serotonin N-acetyltransferase messenger RNA content in rat hippocampus

Background: It has been proposed that up-regulation of cyclic adenosine monophosphate response element binding protein is a common action of chronic antidepressant treatments that may regulate specific target genes in the hippocampus. We hypothesized that the serotonin N-acetyltransferase (AA-NAT; EC 2.3.1.87) gene is one such target. AA-NAT leads to formation of N-acetylserotonin from serotonin, and in the pineal gland, to melatonin synthesis. We investigated whether hippocampal AA-NAT expression can be modified by chronic administration of fluoxetine to rats. Methods: Male Brown-Norway rats were administered 5 mg/kg fluoxetine or its vehicle either once (acute) or once daily for 21 days (chronic). They were sacrificed 18 hours after the last injection, and their hippocampi were processed for a quantitative reverse-transcription/polymerase-chain reaction assay of AA-NAT and cyclophilin (cyc) messenger (m)RNAs. The results are expressed as AA-NAT/cyc ratios. Results: Chronic but not acute fluoxetine administration resulted in about a fivefold increase in hippocampal AA-NAT mRNA. Conclusions: Up-regulation of extrapineal, e.g., hippocampal, AA-NAT expression may play a role in mediating the therapeutic action of antidepressant drugs.