Acute alcohol exposure alters the distribution of alpha4 nicotinic receptors in the mouse brain (Conference Abstract)

A growing body of evidence suggests that nicotinic acetylcholine receptors are important mediators of the effects of alcohol and represent significant pharmacotherapeutic targets for the treatment of alcohol use disorders (AUDs). In particular, the nicotinic alpha4 subunit has been shown to control the brain reward pathway and modulate its response to alcohol. Here we present evidence that a single exposure to alcohol is sufficient to elicit a profound redistribution of alpha4 subunits within the mouse brain reward circuit, including prefrontal-subcortical circuits. Using intraperitoneal bolus injection of a sedative dose of ethanol (3.6 g/kg) in alpha4-YFP transgenic mice, we have quantified the changes in the expression of nicotinic alpha4 subunits by using a combination of western blots and immunohistological techniques combined with 3D reconstruction. Our results show that 24 hr after a single ethanol injection, the expression of alpha4-containing nicotinic receptors is significantly upregulated in the nucleus accumbens (217%) and the amygdala (175%) but not in the prefrontal cortex. This data suggests that acute alcohol exposure alters alpha4 nicotinic receptor signalling principally in the mesolimbic pathway which in turn, might modulate the activity of several neuronal pathways in this brain region.