Short-term fluoxetine treatment alters monoamine levels and turnover in discrete brain nuclei.
The effects of short-term fluoxetine administration on monoamine levels and turnover were assessed in discrete brain nuclei. Adult male rats received fluoxetine HCl (10 mg/kg) or saline injections intraperitoneally for 4 days and monoamine levels determined by high performance liquid chromatography. The major metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), was decreased by fluoxetine treatment in the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area and the CA1 region of the hippocampus. Fluoxetine treatment significantly increased serotonin (5-HT) levels in the VMN but did not change 5-HT levels in any other area examined. Norepinephrine (NE) levels were higher in fluoxetine-treated rats in the dorsomedial hypothalamic nucleus, dorsal raphe nucleus and parietal motor cortex (MCTX). 5-HT and NE turnover were also determined by the pargyline method. Fluoxetine treatment decreased 5-HT turnover in the VMN and increased 5-HT turnover in the median raphe. NE turnover was decreased in the preoptic area, the MCTX and parietal sensory cortex by fluoxetine administration. These results demonstrate that brain areas with similar 5-HT innervation respond differently to fluoxetine administration and fluoxetine, which selectively alters 5-HT uptake, also affects NE levels and turnover in several brain nuclei.
Frankfurt
M
M
Department of Neuroendocrinology, Rockefeller University, New York, NY 10021.
McKittrick
C R
CR
Luine
V N
VN
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D015306:Biogenic Monoamines; D005473:Fluoxetine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009638:Norepinephrine