Mitogen-activated and extracellular regulated kinase (MEK) and extracellular signal-regulated protein kinase (ERK) pathways may underlie ethanol-induced neuroplasticity. Here, the MEK inhibitor UO126 was used 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 c-fos expression in brain regions associated both with rewarding and stressful ethanol actions. Under non-dependent conditions, alcohol-induced c-fos expression was generally not affected by MEK inhibition, with the exception of medial amygdala (MeA), and a similar pattern in the paraventricular nucleus (PVN). In contrast, following a history of dependence, a markedly suppressed c-fos response to acute ethanol was found in orbitofrontal cortex (OFC) and nucleus accumbens shell (AcbSh), key components of circuitry mediating positive drug reinforcement. The suppressed ethanol response in these regions was returned to normal by pre-treatment with UO126, demonstrating a recruitment of an ERK mediated inhibitory regulation in the post-dependent state. Conversely, in brain areas involved in stress responses (MeA, PVN), a MEK/ERK mediated cellular activation by acute ethanol was lost following a history of dependence. These data reveal highly region-specifi c neuroadaptations encompassing the MEK/ERK pathway in ethanol dependence. Recruitment of MEK/ERK mediated suppression of the ethanol response in OFC and AcbSh may refl ect devaluation of ethanol as a reinforcer, while loss of a MEK/ERK mediated response in MeA and PVN may reflect tolerance to its aversive actions. These two neuroadaptations could act in concert to facilitate progression into ethanol dependence.

A.C. Hansson, R. Rimondini, O. Neznanova, W.H. Sommer, M. Heilig (2007). RECRUITMENT OF INHIBITORY MEK/ERK SIGNALING IN BRAIN REWARD CIRCUITRY FOLLOWING A HISTORY OF ETHANOL DEPENDENCE. Ivan Diamond.

RECRUITMENT OF INHIBITORY MEK/ERK SIGNALING IN BRAIN REWARD CIRCUITRY FOLLOWING A HISTORY OF ETHANOL DEPENDENCE

RIMONDINI GIORGINI, ROBERTO;
2007

Abstract

Mitogen-activated and extracellular regulated kinase (MEK) and extracellular signal-regulated protein kinase (ERK) pathways may underlie ethanol-induced neuroplasticity. Here, the MEK inhibitor UO126 was used 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 c-fos expression in brain regions associated both with rewarding and stressful ethanol actions. Under non-dependent conditions, alcohol-induced c-fos expression was generally not affected by MEK inhibition, with the exception of medial amygdala (MeA), and a similar pattern in the paraventricular nucleus (PVN). In contrast, following a history of dependence, a markedly suppressed c-fos response to acute ethanol was found in orbitofrontal cortex (OFC) and nucleus accumbens shell (AcbSh), key components of circuitry mediating positive drug reinforcement. The suppressed ethanol response in these regions was returned to normal by pre-treatment with UO126, demonstrating a recruitment of an ERK mediated inhibitory regulation in the post-dependent state. Conversely, in brain areas involved in stress responses (MeA, PVN), a MEK/ERK mediated cellular activation by acute ethanol was lost following a history of dependence. These data reveal highly region-specifi c neuroadaptations encompassing the MEK/ERK pathway in ethanol dependence. Recruitment of MEK/ERK mediated suppression of the ethanol response in OFC and AcbSh may refl ect devaluation of ethanol as a reinforcer, while loss of a MEK/ERK mediated response in MeA and PVN may reflect tolerance to its aversive actions. These two neuroadaptations could act in concert to facilitate progression into ethanol dependence.
2007
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
78A
78A
A.C. Hansson, R. Rimondini, O. Neznanova, W.H. Sommer, M. Heilig (2007). RECRUITMENT OF INHIBITORY MEK/ERK SIGNALING IN BRAIN REWARD CIRCUITRY FOLLOWING A HISTORY OF ETHANOL DEPENDENCE. Ivan Diamond.
A.C. Hansson; R. Rimondini; O. Neznanova; W.H. Sommer; M. Heilig
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/112500
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