ERK activation induced by fear conditioning in ethanol withdrawn rats: modulation by MK-801

BERTOTTO ME, BIGNANTE EA, GOROSITO SV, CAMBIASSO MJ,MOLINA VA, MARTIJENA ID.

Huerta Grande-Córdoba-Argentina

Congreso; First joint meeting of the Argentine Society for Neurosciences (SAN) and the Argentine workshop in Neurosciences (TAN).; 2009

ERK ACTIVATION INDUCED BY FEAR CONDITIONING IN ethanol withdrawN RATS: MODULATION by MK-801

 

M.E. Bertotto¹, E.A. Bignante¹, S.V. Gorosito², M.J. Cambiasso², V.A. Molina¹, I.D. Martijena¹.

¹ IFEC-CONICET, Dpto. de Farmacología, Facultad de Ciencias Químicas, U.N.C.

² INIMEC-CONICET, Instituto de Investigación Médica Mercedes y Martín Ferreyra.

 Córdoba, Argentina. e-mail: mebertotto@fcq.unc.edu.ar

 

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) the ERK1/2 activation 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hippocampus (dHip) and 2) the effect of NMDA receptor antagonist MK-801 on fear conditioning and ERK activation in ETOH withdrawn rats.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 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High basal levels of pERK1/2 were found in CeA and dHip from ETOH withdrawn rats. ERK activation was significantly increased both in control (60 min) and ETOH withdrawn rats (30 and 60 min) in BLA after fear conditioning.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in control rats, prevented the increase in ERK phosphorylation in BLA and attenuated the freezing response in ETOH withdrawn rats.

These results suggest that the increased fear in ETOH withdrawn rats may be explained by changes in ERK1/2 phosphorylation that depend on NMDA receptor activation in BLA, a structure critically involved in the processing of emotional information.