DIFFERENTIAL EFFECTS OF ETHANOL AND MIDAZOLAM IN THE DEVALUATION OF AN

PAUTASSI, R.M.; NIZHNIKOV, M.; MOLINA, J.C.; SPEAR, N.E.

Chicago, Illinois, EEUU

Congreso; 2007 Annual Meeting of the Research Society on Alcoholism.; 2007

Research Society on Alcoholism

The hedonic content of associative memories is likely to be revaluated through post-acquisition experiences comprising the original unconditioned stimulus (US). For example, 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 devalue conditioning mediated by aversive properties of citric acid (Pautassi et al., 2006). This may be explained by early anxiolytic properties of EtOH. The present set of experiments examined possible mechanisms underlying this antianxiety effect of EtOH. EtOH’s devaluation effects were compared with those of midazolam (MDZ), a fast-acting GABA-A agonist. EtOH and MDZ doses known to exert similar inhibitory effects upon ultrasound vocalizations elicited by citric acid were employed in this study (Nizhnikov et al., 2006). On postnatal day 14 (PD 14) pups were exposed to lemon odor paired with intraoral infusions of citric acid (US). Controls experienced both stimuli in an explicitly unrelated fashion. On PD 15 pups were re-exposed to the citric acid five minutes after being administered either 0.5 g/kg EtOH (i.g), 0.09 mg/kg MDZ (i.p.) or the corresponding vehicle for each drug. Pups were then evaluated in a two-way odor preference test (lemon vs. cineole). Both vehicle and MDZ-treated animals rejected the lemon CS. The aversive 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. In a second experiment a higher dose of MDZ (0.18 mg/kg, i.p) was also found to be ineffective in attenuating the aversive memory. These results indicate that EtOH’s devaluating capabilities are not shared by MDZ and hence appear not to be mediated by GABA. Appetitive motivational properties of EtOH or non-GABAmediated antianxiety effects could be underlying this devaluation effect of ethanol.