ERK activation induced by fear conditioning in ethanol withdrawn rats: modulation by MK-801

BERTOTTO, M.E.; BIGNANTE, E.A.; GOROSITO, S.V.; CAMBIASSO, M.J.; MOLINA, V.A.; MARTIJENA, I.E.

Huerta Grande, Córdoba, Argentina

Congreso; 1ra Reunión Conjunta de Neurociencias organizado por el Taller Argentino de Neurociencias (TAN) y la Sociedad Argentina de Investigación en Neurociencias; 2009

The extracellular signal-regulated kinase (ERK) pathway has been shown to be involved in drug addiction and memory formation. This pathway  is regulated by NMDA receptor activation. We have shown that withdrawal from chronic ETOH administration results in a clear enhancement of contextual fear conditioning. In order to explore the neural substrates and the potential mechanism involved in the increased contextual fear response we examined: 1) (ERK1/2 activation) the activation of ERK1/2  in the central (CeA) and basolateral (BLA) nuclei of the amygdala and in the dorsal hippocampus (dHip) and 2) the effect of NMDA receptor antagonist MK-801 on fear conditioning and ERK activation in ETOH withdrawn rats. Male Wistar rats were made dependent via an ETOH-containing liquid diet (6% v/v) for 14 days. Rats were injected with MK-801 (0.1 mg/kg ip) 30 min prior to contextual fear conditioning on day 3 of ETOH withdrawal.  Half of the rats were sacrificed for Western blot assay at different time points after fear conditioning and the other half was behaviourally evaluated in the conditioned context 24 h later. High basal levels of pERK1/2 were found in CeA and dHip from ETOH withdrawn rats. ERK activation was significantly increased both in control (60 min) and ETOH withdrawn rats (30 and 60 min) in BLA after fear conditioning. MK-801, at a dose that had no effect in control rats, prevented the increase in ERK phosphorylation in BLA and attenuated the freezing response in ETOH withdrawn rats. These results suggest that the increased fear in ETOH withdrawn rats may be explained by changes in ERK1/2 activation that depend on NMDA receptor in BLA, a structure critically involved in the processing of emotional information.