SHORT-TERM FLUOXETINE TREATMENT ALTERS MONOAMINE LEVELS AND TURNOVER IN DISCRETE BRAIN NUCLEI

The effects of short-term fluoxetine administration on monoamine level s and turnover were assessed in discrete brain nuclei. Adult male rats received fluoxetine HCl (10 mg/kg) or saline injections intraperitone ally for 4 days and monoamine levels determined by high performance li quid chromatography. The major metabolite of 5-HT, 5-hydroxyindoleacet ic acid (5-HIAA), was decreased by fluoxetine treatment in the ventrom edial hypothalamic nucleus (VMN), the lateral hypothalamic area and th e CA1 region of the hippocampus. Fluoxetine treatment significantly in creased serotonin (5-HT) levels in the VMN but did not change 5-HT lev els in any other area examined. Norepinephrine (NE) levels were higher in fluoxetine-treated rats in the dorsomedial hypothalamic nucleus, d orsal raphe nucleus and parietal motor cortex (MCTX). 5-HT and NE turn over were also determined by the pargyline method. Fluoxetine treatmen t decreased 5-HT turnover in the VMN and increased 5-HT turnover in th e median raphe. NE turnover was decreased in the preoptic area, the MC TX and parietal sensory cortex by fluoxetine administration. These res ults demonstrate that brain areas with similar 5-HT innervation respon d differently to fluoxetine administration and fluoxetine, which selec tively alters 5-HT uptake, also affects NE levels and turnover in seve ral brain nuclei.