Modulation of fear conditioning by MK-801 in ethanol withdrawn rats

BERTOTTO ME, BOIERO C, MOLINA VA, MARTIJENA ID

Tandil, Argentina

Congreso; XL Reunión anual de la Asociación Argentina de Farmacología; 2008

Sociedad Argentina de Farmacología Experimental

We have recently shown that discontinuation from chronic ethanol  administration results in a clear enhancement of contextual fear  conditioning. It is known that NMDA receptors are a major site for  ETOH action and that they play a critical role in memory processes and  in associative aversive learning. Therefore, in the present study we  investigated the effect of MK-801, a NMDA receptor antagonist, on fear  conditioning in ETOH withdrawn rats.Wistar rats made dependent via an etanol (6% v/v) containing liquid  diet for 14 days. Three days after the last ethanol administration  animals were injected with MK-801 (0.1 mg/kg i.p.) 30 min before a  contextual fear conditioning paradigm (3 electrical foot-shocks 0.4mA,  duration 3s; ITI: 30s). Twenty-four hours later animals were exposed  to the context without shock delivery and the freezing response was  evaluated.The present study shows that: 1). The formation of a new fear memory  is facilitated in animals that have previously experienced ETOH  withdrawal. 2). Administration of MK-801, at a dose that did not  affect the acquisition of contextual fear conditioning in control  animals, normalized the freezing response in ETOH withdrawn rats. 3).  0.3 mg/kg seems to be an effective dose of MK-801 to block the  fear  conditioning acquisition in control rats.The enhanced sensitivity to the facilitatory effect  of MK-801 in ETOH  withdrawn animals may be mediated by adaptive changes in NMDA  receptors provoked by ETOH dependence.