CONICET | Buscador de Institutos y Recursos Humanos

Aversive memories acquired through pairings of a conditioned (CS) and an unconditioned stimulus (US) are susceptible to modification after initial acquisition. Further pairings of the original US with an alternative US of opposite hedonic value results in a reduced (i.e., devalued) conditioned response. In infant rats, low doses of ethanol (EtOH, 0.25 1.25 g/kg) have been found to attenuate effect of an aversive US (Pautassi et al., 2006). This may be explained by early anxiolytic properties of EtOH. The present set of experiments aimed to analyze the mechanisms underlying this putative antiaxiety effect of EtOH. Specifically, EtOHs effects in the devaluation technique were compared with those of midazolam (MDZ), a fast-acting GABA-A agonist. Drug dosage was equated in terms of behavioral effects on the expression of citric acid-induced distress calls (Nizhnikov et al., 2006). Four conditioning trials were conducted on postnatal day 14 (P14), each defined by a 5-minute exposure to a lemon odor (CS) paired with intraoral pulsate infusion of citric acid (US). Control animals experienced both stimuli in an explicitly unrelated fashion. On PD 15 pups were briefly exposed to the citric acid solution five minutes after being administered either 0.5 g/kg EtOH, i.g, 0.09 mg/kg MDZ, i.p or the respective vehicle for each drug. Pups were assessed in a two-way odor preference test (lemon vs. cineole) 120 minutes later. Both vehicle and MDZ-treated animals spent significantly less time near the lemon CS, thus expressing a citric-acid mediated odor aversion. This conditioned response was completely inhibited in pups that received 0.5 g/kg EtOH. Locomotor patterns at test were not affected by either EtOH or MDZ administration. A higher dose of MDZ (0.18 mg/kg, i.p) was also ineffective in attenuating the aversive memory as seen in a later experiment. To sum up, EtOHs devaluating capabilities are not shared by MDZ, indicating that these effects of EtOH are not GABA-mediated. Appetitive motivational properties of EtOH or non-GABA-mediated antianxiety effects (i.e, NMDA-related) could be underlying this devaluation effect of ethanol.

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