Acute effect of 17 beta-estradiol and lithium on ovariectomized rat brain biogenic amines metabolism.
The effect of 17 beta-estradiol (E2) on the response of dopamine (DA) and serotonin (5-HT) to acute lithium in the brains of ovariectomized rats was investigated. An E2 injection (100 ng/s.c.) to ovariectomized rats did not change striatal DA levels, whereas the levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), increased 30 min later; concentrations of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), also remained unchanged. In the frontal cortex, DA, 5-HT, HVA and 5-HIAA levels remained unchanged after the E2 injection, whereas DOPAC levels and DOPAC/DA and HVA/DA ratios increased 30 min later. Injection of LiCl (10 mEq) decreased striatal DA levels, increased DOPAC levels and slightly decreased HVA levels; by contrast, frontal cortex DA and HVA levels increased but DOPAC levels were unchanged. A biphasic response of striatal 5-HT levels occurred, increasing shortly after injection of LiCl, followed by a decrease; 5-HIAA levels, however, increased. In the frontal cortex, injection of rats with LiCl led to a gradual increase in 5-HT levels, whereas 5-HIAA concentrations decreased. In the presence of E2, LiCl effected a greater decrease in striatal DA than injection of LiCl alone, advanced the DOPAC peak by 30 min and increased HVA levels; E2 had less effect on the 5-HT response to LiCl, except the decreases in 5-HT and 5-HIAA at 60 min were greater. Furthermore, in the striatum, the increased DA turnover caused by LiCl, estimated by the DOPAC/DA and HVA/DA ratios, was advanced in rats treated with E2. In the presence of E2, LiCl slightly increased frontal cortex DA, DOPAC and HVA levels compared with treatment with LiCl alone, whereas DOPAC levels decreased in rats treated with LiCl + E2 compared with levels in E2-treated rats. Generally, higher levels of 5-HT and 5-HIAA were measured in the frontal cortices of rats treated with LiCl + Ex compared with rats injected with LiCl. These results indicate that E2 potentiates the acute effect of lithium on striatal and frontal cortex DA and 5-HT levels and metabolism, suggesting a role of the hormonal state on this drug response.
Morissette
M
M
School of Pharmacy, Laval University, Québec, Canada.
Paolo
T D
TD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D004958:Estradiol; D006897:Hydroxyindoleacetic Acid; D018021:Lithium Chloride; D004298:Dopamine; D006719:Homovanillic Acid