Intra-amygdala inhibition of ERK1/2 potentiates the discriminative stimulus effects of alcohol

作者: Joyce Besheer , Kristen R. Fisher , Reginald Cannady , Julie J.M. Grondin , Clyde W. Hodge

DOI: 10.1016/J.BBR.2011.12.023

关键词: Stimulus controlMAPK/ERK pathwayMicroinjectionNucleus accumbensKinasePharmacologyAlcoholPsychologyAmygdalaEthanol

摘要: Extracellular signal-regulated kinase (ERK1/2) has been implicated in modulating drug seeking behavior and is a target of alcohol other drugs abuse. Given that the discriminative stimulus (subjective/interoceptive) effects are determinants abuse liability can influence behavior, we examined role ERK1/2 alcohol. Using discrimination procedures, rats were trained to discriminate moderate intragastric (IG) dose (1 g/kg) versus water (IG). Following an session phosphorylated (pERK1/2) immunoreactivity (IR) was significantly elevated amygdala, but not nucleus accumbens. Therefore, hypothesized intra-amygdala inhibition would disrupt expression However, or accumbens administration MEK/ERK1/2 inhibitor U0126 3 μg) had no effect on training g/kg). Contrary our hypothesis, infusion (3 potentiated low (0.5 following infusion. Importantly, site-specific pERK1/2 each brain region confirmed. increase IR amygdala systemic may be reflective widespread (activation/inhibition circuits), whereas site specific microinjection studies confirmed functional involvement ERK1/2. These findings show activity ERK signaling pathway

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