A considerable amount of experimental evidence has demonstrated ethanol (EtOH) induced amnestic effects following EtOH administration during pretraining in a variety of tasks both in humans and in laboratory animals. Although the phenomenon of state-dependency is known to play a critical role in memory deficits induced by both pharmacological and nonpharmacological pretraining perturbations, the involvement of this phenomenon in EtOH-induced anterograde amnesia has been overlooked. This study aimed to investigate the role of state-dependency in EtOH-induced amnestic effects and its interactions with the well-known anxiolysis and locomotor alterations.
Mice were treated with 1.2 or 2.4 g/kg EtOH before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behavior, and general activity.
Whereas both doses of EtOH induced anxiolysis, the 1.2 g/kg dose enhanced locomotion while the 2.4 g/kg dose decreased it. In addition, the administration of 1.2 g/kg of this drug during pretraining caused memory impairment, which was counteracted by the pretest administration of the same dose, revealing the participation of the state-dependency. Conversely, the administration of 2.4 g/kg EtOH led to amnestic effects irrespective of the time of the administration (pretraining and/or pretest), eliminating the influence of state-dependency.
Our data demonstrate that EtOH-induced memory deficits are critically related to state-dependency, which can also be affected by the dose range. These results indicate the possible participation of EtOH-induced modifications in anxiety and motor activity levels in relation to state-dependent memory deficits.