Review articleEffects of ethanol on an acetaldehyde drug discrimination with a conditioned taste aversion procedure
Introduction
The proximate product of ethanol metabolism, acetaldehyde, has been proposed to play a role in mediating several ethanol-related behaviors and voluntary ethanol consumption [for review, see Smith et al. (1997)]. It is thought that ethanol is metabolized in brain into acetaldehyde, where it then exerts its effects on ethanol intake and ethanol-related behaviors. The enzyme catalase is capable of metabolizing ethanol into acetaldehyde in brain (Cohen et al., 1980). More importantly, it has been shown that catalase may be the major route for ethanol metabolism in the brain with little or no contribution of alcohol dehydrogenase or cytochrome P450 2EI (Gill et al., 1992).
Work from this laboratory has provided evidence that catalase plays an important role in mediating ethanol-related behaviors. A positive correlation between catalase activity and voluntary ethanol consumption has been reported in both human beings Amit et al. 1999, Koechling & Amit 1992, Koechling et al. 1995 and rats Amit & Aragon 1988, Aragon et al. 1985b, Gill et al. 1996. These findings support the suggestion that catalase may be important in mediating ethanol consumption. Further support for this notion was attained when pretreatment with 3-amino-1,2,4-triazole (AT), a catalase inhibitor, attenuated the acquisition (Rotzinger et al., 1994) and maintenance Aragon & Amit 1992, Koechling & Amit 1994 of voluntary ethanol consumption. In addition to decreasing ethanol consumption, AT administration has been shown to attenuate several ethanol-induced behaviors, such as a conditioned taste aversion (Aragon et al., 1985a), locomotor depression (Aragon et al., 1991a), narcosis, and lethality (Aragon et al., 1991b), further supporting the hypothesis that catalase and acetaldehyde play an important role in behaviors induced by ethanol.
The hypothesis that acetaldehyde may play a role in mediating some of the actions of ethanol can be inferred from results of self-administration studies. Several researchers have shown in these studies that rats will self-administer acetaldehyde intravenously Myers et al. 1982, Myers et al. 1984, intracerebroventricularly Brown et al. 1979, Brown et al. 1980, and intracerebrally into the posterior ventral tegmental area (Rodd-Henricks et al., 2000).
Drug-discrimination paradigms have been long used as a tool to investigate the stimulus properties of psychoactive drugs, including ethanol. These drug-discrimination studies are typically conducted in operant chambers fitted with two levers. An animal is trained to discriminate the presence of ethanol from saline. When the training drug is administered, the subject is trained to press a designated lever (the drug lever) to receive some sort of reinforcer (usually food pellets or some type of fluid). When the vehicle is administered the subject is trained to press the other lever to obtain the reinforcer. Once stimulus control has been achieved, substitution (administration of other drugs) or antagonism tests can be performed. One disadvantage of this procedure is that it often takes a long time for the subject to acquire lever pressing and stimulus control (Järbe et al., 1982).
A novel paradigm for investigating drug discrimination has been used for training and acquisition of stimulus control of a training drug in a relatively shorter time frame than with traditional operant paradigms. In this particular drug-discrimination procedure, a conditioned taste aversion procedure is used Herrera & Velazquez Martinez 1997, Lucki 1988, Revusky et al. 1982, Smurthwaite & Riley 1994, Stevenson et al. 1992. Subjects are trained to associate the training drug with either an aversive state (produced by injections of LiCl) or no aversive state (saline injections). The procedure consists of pairing of the target drug with either LiCl or saline and then measuring the amount of a saccharin-flavored solution consumed. It is assumed that subjects learn to associate the training drug, and its stimulus properties, with the taste-toxin pairing of LiCl, producing a decrease in saccharin intake. On days on which saline is administered before the saccharin solution, subjects should not associate any adverse effects and thus readily consume saccharin.
Results of recent work in this laboratory have shown that the discriminative taste aversion procedure can be used to train animals to discriminate ethanol from saline (Redila et al., 2000). In that study, animals learned to discriminate ethanol (0.8 g/kg) from saline and that acetaldehyde will produce ethanol-like behavior. That is, acetaldehyde may be generalized partially to ethanol. The purpose of the current study was to examine whether acetaldehyde could be used successfully as the stimulus drug with the use of the discriminative taste aversion procedure and whether ethanol will generalize to acetaldehyde.
Section snippets
Subjects
Thirty-two, male, Long–Evans rats, each weighing between 225 and 250 g at the start of the experiment, were used and housed individually in stainless steel hanging cages. Animals were kept in a colony room maintained at a constant temperature and on a 12-h:12-h light:dark cycle (lights on at 0800). The care and use of animals, as well as the methods used, were in compliance with and approved by the Concordia University Animal Care Committee.
Drugs
A 5% (vol./vol.) acetaldehyde solution (Aldrich
Results
During acquisition of the acetaldehyde discriminative taste aversion, several animals became ill and were subsequently dropped from the study. One animal from the 0.2-g/kg Acet–Saline training dose group, and a total of five animals from one of the 0.3-g/kg training dose groups—two from the Acet–LiCl training dose group and three from the Acet–Saline training dose group—failed to complete the study. In addition, one animal from each of the Acet–LiCl training dose groups failed to satisfy the
Discussion
In the current study, we used a discriminative taste aversion procedure to examine whether ethanol would generalize to an acetaldehyde drug discrimination; that is, whether acetaldehyde and ethanol share similar stimulus properties. Findings obtained from the conditioning phase of the study showed that animals were able to discriminate acetaldehyde from saline after the eight training cycles. Results of the ethanol generalization tests revealed a similar pattern for both training doses of
Acknowledgements
This research was partially funded by a grant from the Medical Research Council of Canada to ZA and BRS.
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