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)

Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction.

The effects of pimozide were examined in a runway paradigm using food reward. Rats received one of three doses of pimozide, vehicle or Ringer's prior to testing. Two additional groups received pimozide or vehicle after the test trial in the home cage. An extinction group received no food in the goal box on test days. Several components of running behavior were assessed as was food consumed in the goal box. Effects of pimozide on general locomotor activity were assessed in the open-field following the runway phase. Results of the runway indicated that pimozide-treated rats differed from the extinction group in latencies to leave the start box and enter the goal box. Pimozide-treated rats consumed less saccharin-flavored food than controls. The post-treatment pimozide group showed a reduction in saccharin-food intake suggesting a conditioned taste aversion. Thus, the reduction observed in the pretreated pimozide group may be due to some unconditioned aversion induced by the drug. Open-field revealed that pimozide resulted in lower activity than controls. This study indicates that the effects of pimozide on food reinforcement are not similar to the effects seen in extinction. These data are consistent with the hypothesis that the effects of pimozide, in this paradigm, constitute an interference with motor responses as opposed to an attenuation of reward properties of the stimuli.