RESUMEN
Experimental evidence indicates that anesthetic doses of the non-competitive NMDA receptor antagonist ketamine impair memory abilities in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. In this context, it has been proposed that the effects of anesthetic ketamine on memory might be attributed to its agonistic properties on the GABA type A receptor. The present study was designed to address this issue. Thus, we investigated the ability of the benzodiazepine receptor antagonist flumazenil (1, 3, 6â¯mg/kg, i.p.) and the GABAA receptor antagonist bicuculline (0.5, 1.5, 3â¯mg/kg, i.p.) to counteract recognition memory deficits produced by anesthetic ketamine (100â¯mg/kg, i.p.) in rats. For this purpose, the novel object recognition task, a behavioural paradigm assessing recognition memory abilities in rodents was used. Compounds were coadministered 24â¯h before testing or retention. Pre (24â¯h before testing) or post-training (24â¯h before retention) administration of flumazenil (6â¯mg/kg, i.p.) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. Conversely, bicuculline failed to attenuate the recognition memory deficits caused by anesthetic ketamine. Our findings propose a functional interaction between anesthetic ketamine and the GABAA receptor allosteric modulator flumazenil on recognition memory.