Baclofen alters gustatory discrimination capabilities and induces a conditioned taste aversion (CTA)

Abstract

Background: Studies intending to measure drug-induced changes in learning and memory are challenged to parse out the effects of drugs on sensory, motor, and associative systems in the brain. In the context of conditioned taste aversion (CTA), drugs that alter the sensorium of subjects and affect their ability to taste and/or feel malaise may limit the ability of investigators to make conclusions about associative effects of these substances. Since the GABAergic system is implicated in inhibition, the authors were hopeful to use the GABA agonist, baclofen (BAC), to enhance extinction of a CTA, but first a preliminary evaluation of BAC's peripheral effects on animals' sensorium had to be completed due to a lack of published literature in this area.

Findings: Our first experiment aimed to evaluate the extent to which the GABAB agonist, BAC, altered the ability of rats to differentiate between 0.3% and 0.6% saccharin (SAC) in a two bottle preference test. Here we report that 2 or 3 mg/kg (i.p.) BAC, but not 1 mg/kg BAC, impaired animals' gustatory discrimination abilities in this task. Furthermore, when SAC consumption was preceded by 2 or 3 mg/kg (i.p.) BAC, rats depressed their subsequent SAC drinking.A second experiment evaluated if the suppression of SAC and water drinking (revealed in Experiment 1) was mediated by amnesiac effects of BAC or whether BAC possessed US properties in the context of the CTA paradigm. The time necessary to reach an asymptotic level of CTA extinction was not significantly different in those animals that received the 3 mg/kg dose of BAC compared to more conventionally SAC + lithium chloride (LiCl, 81 mg/kg) conditioned animals.

Conclusions: Our findings were not consistent with a simple amnesia-of-neophobia explanation. Instead, results indicated that 2 and 3 mg/kg (i.p.) BAC were capable of inducing a CTA, which was extinguishable via repeated presentations of SAC only. Our data indicate that, depending on the dose, BAC can alter SAC taste discrimination and act as a potent US in the context of a CTA paradigm.

Figure 1

Experiment 1-Evaluation of 0.3% versus 0.6% SAC Discrimination. Mean ml SAC Consumption (± SEM) on the First Taste Exposure Day and both SAC Discrimination Test Days. RM-ANOVA showed that on the First Taste Exposure, in the absence of any drug treatment or other behavioral manipulation, all animals drank significantly more 0.3% SAC in comparison to 0.6% SAC. Also, RM-ANOVA showed that on both SAC Discrimination Test Days the SAL and BAC 1 mg/kg groups drank significantly more 0.3% SAC than 0.6% SAC. The BAC 2 mg/kg and BAC 3 mg/kg groups did not drink significantly different amounts of 0.3% SAC and 0.6% SAC on either test day. The SAL and BAC 1 mg/kg groups also showed a steady increase in 0.3% SAC consumption between the First Taste Exposure and Test 2 (the final taste exposure), but the BAC 2 mg/kg and BAC 3 mg/kg groups did not increase their consumption of 0.3% SAC. * Significant within group difference between 0.3% and 0.6% SAC. p < 0.05

Figure 2

Experiment 2-CTA Acquisition. Mean ml SAC. Consumption (± SEM) on the Final Acquisition Trial. All animals that received either SAC + LiCl or SAC + BAC pairings acquired a strong taste aversion to SAC by the third CTA trial, as illustrated by the significant difference in SAC drinking between animals given EU training and those that had SAC paired with LiCl or BAC. All of the EU groups that did not receive CS + US pairings did not acquire a CTA, as indicated by high SAC drinking on trail 3, which was significantly greater than their drinking on trial 1. The SAC + LiCl, SAC + BAC 2 mg/kg and SAC + BAC 3 mg/kg groups were all drinking near-zero amounts of SAC on trial 3, which was significantly less than their SAC drinking on trial 1. Drinking on the first conditioning trial was not significantly different between any groups [Mean SAC consumption ± SEM on trial 1 = 4.35 ± 1.22 ml]. Note: A BAC 1 mg/kg group was not used in Experiment 2 because this group did not indicate a disruption of SAC discrimination capabilities in Experiment 1 nor did they demonstrate any possible US effects of BAC exposure in Experiment 1. *Significant difference between EU groups and the following CS + US groups: SAC + LiCl, SAC + BAC 2 mg/kg, and SAC + BAC 3 mg/kg. p < 0.05

Figure 3

Experiment 2-CS-Only Extinction. Mean Days (± SEM) to Asymptotic EXT. The LiCl and BAC 3 mg/kg groups did not differ significantly in the number of days required to reach asymptotic EXT. However, the BAC 2 mg/kg group extinguished significantly faster than the LiCl and BAC 3 mg/kg groups. * Significantly less than both LiCl and BAC 3 mg/kg groups. p < 0.05