Suppression of voluntary ethanol consumption in rats by gamma-butyrolactone.
The effect of gamma-butyrolactone (GBL) on voluntary ethanol intake was studied in a group of Wistar rats in which a stable preference had been induced by exposure to increasing ethanol concentrations. These rats drank 60% of their daily fluid intake as 15% ethanol solution, corresponding to about 6 g ethanol/kg/day. GBL, injected intraperitoneally at the dose of 200 mg/kg, twice daily for 3 consecutive days, decreased ethanol intake by about 80% on the days of treatment, but did not reduce total fluid intake. Ethanol intake remained significantly reduced up to the 5th day following cessation of GBL administration. GBL, up to a concentration of 10(-3) M, inhibited neither alcohol-dehydrogenase nor aldehyde-dehydrogenase in rat liver homogenates, nor dopamine-beta-hydroxylase in homogenates of adrenal medulla or hypothalamus of rats. It is suggested that inhibition of firing in dopaminergic neurons mediates the suppressant effect of GBL on ethanol preference.
D015107:4-Butyrolactone / Q000494:pharmacology*; D000311:Adrenal Glands / Q000201:enzymology; D000426:Alcohol Dehydrogenase; D000428:Alcohol Drinking / Q000187:drug effects*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D007031:Hypothalamus / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005663:Furans; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D004299:Dopamine beta-Hydroxylase; D015107:4-Butyrolactone; D004298:Dopamine