MODULATION of FEAR conditioning by MK-801 IN ethanol withdrawN RATS.
M.E. Bertotto, C. Boiero, V.A. Molina, I.D. Martijena. IFEC-CONICET, Departamernto de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5016 Córdoba, Argentina. mebertotto@fcq.unc.edu.ar
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in the present study we investigated the effect of MK-801, a NMDA receptor antagonist, on fear conditioning in ETOH withdrawn rats.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not affect the acquisition of contextual fear conditioning in control animals, normalized the freezing response in ETOH withdrawn rats. 3). 0.3 mg/kg seems to be an effective dose of MK-801 to block the fear conditioning acquisition in control rats.
The enhanced sensitivity to the facilitatory effect of MK-801 in ETOH withdrawn animals may be mediated by adaptive changes in NMDA receptors provoked by ETOH dependence.
Modo de presentación: POSTER
