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Neuroplasticity in brain reward circuitry following a history of ethanol dependence
Author(s) -
Hansson Anita C.,
Rimondini Roberto,
Neznanova Olga,
Sommer Wolfgang H.,
Heilig Markus
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06159.x
Subject(s) - mapk/erk pathway , nucleus accumbens , amygdala , conditioned place preference , mek inhibitor , ethanol , extracellular , neuroscience , neuroplasticity , chemistry , kinase , microbiology and biotechnology , psychology , endocrinology , medicine , biology , biochemistry , addiction , central nervous system
Mitogen‐activated and extracellular regulated kinase (MEK) and extracellular signal‐regulated protein kinase (ERK) pathways may underlie ethanol‐induced neuroplasticity. Here, we used the MEK inhibitor 1,4‐diamino‐2,3‐dicyano‐1,4‐bis(2‐aminophenylthio)butadiene (UO126) to probe the role of MEK/ERK signaling for the cellular response to an acute ethanol challenge in rats with or without a history of ethanol dependence. Ethanol (1.5 g/kg, i.p.) induced expression of the marker genes c‐fos and egr‐1 in brain regions associated with both rewarding and stressful ethanol actions. Under non‐dependent conditions, ethanol‐induced c‐fos expression was generally not affected by MEK inhibition, with the exception of the medial amygdala (MeA). In contrast, following a history of dependence, a markedly suppressed c‐fos response to acute ethanol was found in the medial pre‐frontal/orbitofrontal cortex (OFC), nucleus accumbens shell (AcbSh) and paraventricular nucleus (PVN). The suppressed ethanol response in the OFC and AcbSh, key regions involved in ethanol preference and seeking, was restored by pre‐treatment with UO126, demonstrating a recruitment of an ERK/MEK‐mediated inhibitory regulation in the post‐dependent state. Conversely, in brain areas involved in stress responses (MeA and PVN), an MEK/ERK‐mediated cellular activation by acute ethanol was lost following a history of dependence. These data reveal region‐specific neuroadaptations encompassing the MEK/ERK pathway in ethanol dependence. Recruitment of MEK/ERK‐mediated suppression of the ethanol response in the OFC and AcbSh may reflect devaluation of ethanol as a reinforcer, whereas loss of an MEK/ERK‐mediated response in the MeA and PVN may reflect tolerance to its aversive actions. These two neuroadaptations could act in concert to facilitate progression into ethanol dependence.