Neurotoxicological analyses of voluntary alcohol drinking by the rat.

The enzymes primarily responsible for the metabolism of ethanol and acetaldehyde were studied in distinct rat brain regions as a function of sex, age and preference to voluntary intake of ethanol. The effects of pH of the injectable drug and of ethanol injection on voluntary drinking of diluted ethanol solution over water were also evaluated in the male rat. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities increased in all 5 brain regions studied from 26 days to 67 days of age, as contrasted with an age-dependent decline in these hepatic enzymes. The latter showed sex-linked differences in ADH and ALDH which were absent in the brain. Rats with preference to ethanol showed a moderate increase in brain ADH in diencephalon, cerebellum, mid-brain and pons-medulla regions, in addition to that of ALDH in the mid-brain and pons-medulla areas compared to controls or to rats avoiding selection of ethanol. Injection of 3-O-methyl dopa at acidic pH or 0.1 N HCl, but not the same drug dosage at neutral pH or saline, resulted in reduction of voluntary drinking of ethanol by the male rat. Likewise, injection of 25% ethanol, 1 g/kg, IP, decreased ethanol selection for drinking. No measureable blood plasma ethanol was detectable in rats with preference to ethanol, consuming approximately 3 g/kg/day in their drinking fluid. The results show lack of similarities between the liver and the brain in the factors studied and indicate some experimental variances in voluntary intake of ethanol by the rat.