The role of acetaldehyde-metabolizing enzymes in the mediation of ethanol consumption: an investigation using a simulated drinking bout.

Laboratory rats in a 24 hr free choice paradigm consume ethanol in a series of discrete drinking bouts. However, little research has been directed at establishing whether these individual bouts were pharmacologically relevant to animals. The present study was designed to investigate the pharmacological efficacy of a simulated ethanol drinking bout and the possible role of acetaldehyde (ACH) and its metabolizing enzymes in mediating these effects using various enzyme manipulations. Following an ethanol screening procedure (2% to 10%, free choice) to establish a drinking baseline, animals were deprived of ethanol for a two week period. Using a limited access procedure, animals were then presented with a 10% ethanol solution for a 10 min period each day for 10 days. On Days 11-15, 4 hr prior to ethanol presentation, animals were divided into four groups and received i.p. injections of either saline (S), 4-methylpyrazole (4MP), cyanamide (C) or 4-methylpyrazole + cyanamide (4MP + C). This latter treatment condition has been shown to prevent the accumulation of ACH in the periphery by cyanamide. On Day 12, 10 min after the drinking session, animals were placed in open field chambers and locomotor activity was recorded for 5 min. Results indicated that animals pretreated with cyanamide (groups S + C and 4MP + C) consumed significantly more ethanol across the 5 test days than groups S + S and 4MP + S. Locomotor activity was significantly depressed for animals pretreated with cyanamide alone (C + S), although drinking levels were comparable to all other groups on Day 12. Together, these data demonstrate that a stimulated drinking bout is a pharmacologically meaningful event since it can be altered by manipulating acetaldehyde-metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)