T. Uz et H. Manev, Chronic fluoxetine administration increases the serotonin N-acetyltransferase messenger RNA content in rat hippocampus, BIOL PSYCHI, 45(2), 1999, pp. 175-179
Background: It has been proposed that up-regulation of cyclic adenosine mon
ophosphate response element binding protein is a common action of chronic a
ntidepressant treatments that may regulate specific target genes in the hip
pocampus. We hypothesized that the serotonin N-acetyltransferase (AA-NAT; E
C 2.3.1.87) gene is one such target. AA-NAT leads to formation of N-acetyls
erotonin from serotonin, and in the pineal gland, to melatonin synthesis. W
e investigated whether hippocampal AA-NAT expression can be modified by chr
onic 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 pr
ocessed for a quantitative reverse-transcription/polymerase-chain reaction
assay of AA-NAT and cyclophilin (cyc) messenger (m)RNAs. The results are ex
pressed 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 expres
sion may play a role in mediating the therapeutic action of antidepressant
drugs. (C) 1999 Society of Biological Psychiatry.