title: ERK activation in the amygdala and hippocampus induced by fear conditioning in ethanol withdrawn rats: modulation by MK-801.
abstract: The extracellular signal-regulated kinase (ERK) pathway, which can be activated by NMDA receptor stimulation, is involved in fear conditioning and drug addiction. We have previously shown that withdrawal from chronic ethanol administration facilitated the formation of contextual fear memory. In order to explore the neural substrates and the potential mechanism involved in this effect, we examined: 1) the ERK1/2 activation in the central (CeA) and basolateral (BLA) nuclei of the amygdala and in the dorsal hippocampus (dHip), 2) the effect of the NMDA receptor antagonist MK-801 on fear conditioning and ERK activation and 3) the effect of the infusion of U0126, a MEK inhibitor, into the BLA on fear memory formation in ethanol withdrawn rats. Rats made dependent via an ethanol-containing liquid diet were subjected to contextual fear conditioning on day 3 of ethanol withdrawal. High basal levels of p-ERK were found in CeA and dHip from ethanol withdrawn rats. ERK activation was significantly increased both in control (60min) and ethanol withdrawn rats (30 and 60min) in BLA after fear conditioning. Pre-training administration of MK-801, at a dose that had no effect on control rats, prevented the increase in ERK phosphorylation in BLA and attenuated the freezing response 24h later in ethanol withdrawn rats. Furthermore, the infusion of U0126 into the BLA, but not the CeA, before fear conditioning disrupted fear memory formation. These results suggest that the increased fear memory can be linked to changes in ERK phosphorylation, probably due to NMDA receptor activation in BLA in ethanol withdrawn rats.
authors.affiliation: IFEC-CONICET, Departamento de Farmacología, Universidad Nacional de Córdoba, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Bertotto
authors.forename: Noelia Martina
authors.initials: NM
authors.lastname: Maldonado
authors.forename: Elena Anahi
authors.initials: EA
authors.lastname: Bignante
authors.forename: Silvana Vanesa
authors.initials: SV
authors.lastname: Gorosito
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Cambiasso
authors.forename: Víctor Alejandro
authors.initials: VA
authors.lastname: Molina
authors.forename: Irene Delia
authors.initials: ID
authors.lastname: Martijena
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000201:enzymology / Q000523:psychology
chemical_list: D000431:Ethanol; D016291:Dizocilpine Maleate; D048049:Extracellular Signal-Regulated MAP Kinases