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Alcohol Alters the Activation of ERK1/2, a Functional Regulator of Binge Alcohol Drinking in Adult C57BL/6J Mice
Author(s) -
Agoglia Abigail E.,
Sharko Amanda C.,
Psilos Kelly E.,
Holstein Sarah E.,
Reid Grant T.,
Hodge Clyde W.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12645
Subject(s) - binge drinking , alcohol , nucleus accumbens , mapk/erk pathway , ethanol , prefrontal cortex , addiction , amygdala , endocrinology , medicine , kinase , neuroscience , chemistry , psychology , pharmacology , central nervous system , biochemistry , alcohol consumption , cognition
Background Binge alcohol drinking is a particularly risky pattern of alcohol consumption that often precedes alcohol dependence and addiction. The transition from binge alcohol drinking to alcohol addiction likely involves mechanisms of synaptic plasticity and learning in the brain. The mitogen‐activated protein kinase ( MAPK ) signaling cascades have been shown to be involved in learning and memory, as well as the response to drugs of abuse, but their role in binge alcohol drinking remains unclear. The present experiments were designed to determine the effects of acute alcohol on extracellular signaling‐related kinases ( ERK 1/2) expression and activity and to determine whether ERK 1/2 activity functionally regulates binge‐like alcohol drinking. Methods Adult male C57 BL /6J mice were injected with ethanol (EtOH) (3.0 mg/kg, intraperitoneally ) 10, 30, or 90 minutes prior to brain tissue collection. Next, mice that were brought to freely consume unsweetened EtOH in a binge‐like access procedure were pretreated with the MEK 1/2 inhibitor SL 327 or the p38 MAPK inhibitor SB 239063. Results Acute EtOH increased pERK 1/2 immunoreactivity relative to vehicle in brain regions known to be involved in drug reward and addiction, including the central amygdala and prefrontal cortex. However, EtOH decreased pERK 1/2 immunoreactivity relative to vehicle in the nucleus accumbens core. SB 239063 pretreatment significantly decreased EtOH consumption only at doses that also produced nonspecific locomotor effects. SL 327 pretreatment significantly increased EtOH, but not sucrose, consumption without inducing generalized locomotor effects. Conclusions These findings indicate that ERK 1/2 MAPK signaling regulates binge‐like alcohol drinking. As alcohol increased pERK 1/2 immunoreactivity relative to vehicle in brain regions known to regulate drug self‐administration, SL 327 may have blocked this direct pharmacological effect of alcohol and thereby inhibited the termination of binge‐like drinking.