The GABA Antagonist Picrotoxin Attenuates an Ethanol-Induced Taste Aversion in Taste Aversion-Prone Rats

The aversive properties of alcohol can be examined by using ethanol as a conditioning agent in a taste aversion (TA) paradigm. However, there is often variability in how organisms respond to the aversive properties of alcohol. Using a selectively bred line of TA-prone (TAP) rats, the present study sought to determine if antagonizing the GABA receptor complex with picrotoxin could block the acquisition of an ethanol-based conditioned aversion to a normally preferred fluid. Fifty TAP rats were randomly divided into 5 groups. In the two experimental groups, rats were pretreated with i.p. injections of low or high doses of the GABAA antagonist picrotoxin prior to undergoing taste aversion conditioning —wherein consumption of a novel saccharin solution (0.1%) was followed by an i.p. injection of ethanol (1.5 mg/kg). In the primary control group, rats were treated identically, except that isotonic saline was substituted for picrotoxin. In the non-conditioning and pseudo-conditioning control groups, rats did not receive an ethanol-saccharin pairing but did receive a picrotoxin injection. Repeated measures ANOVA revealed that animals in the picrotoxin groups displayed significantly weaker TAs than the primary control group (p < 0.01), but were not different from the non-conditioning and pseudo-conditioning groups (p > 0.05) as measured by post-conditioning, two-bottle saccharin preference scores. Picrotoxin hinders the acquisition of an ethanol-induced TA, thereby supporting the hypothesis that the GABA system plays a central role in ethanol’s motivational effects. Possible mechanisms include 1) picrotoxin attenuates negative effects of ethanol, 2) picrotoxin interferes with the central associative processes that promote TA conditioning or 3) some combination of 1 and 2.