Chunk #35 — 3 Neural Substrates for the Negative Emotional State Associated with Alcoholism — 3.1 Within-System Neuroadaptations that Contribute to the Compulsivity Associated with the Dark Side of Alcoholism
Other within-system neuroadaptations under this conceptual framework could include increased sensitivity of receptor transduction mechanisms in the nucleus accumbens. Drugs of abuse have acute receptor actions that are linked to intracellular signaling pathways that may undergo adaptations with chronic treatment. In the context of chronic alcohol administration, multiple molecular mechanisms have been hypothesized to counteract the acute effects of ethanol that could be considered within-system neuroadaptations. For example, chronic ethanol decreases γ-aminobutyric acid (GABA) receptor function, possibly through downregulation of the α1 subunit (Mhatre et al. 1993; Devaud et al. 1997). Chronic ethanol also decreases the acute inhibition of adenosine reuptake (i.e., tolerance develops to the inhibition of adenosine by ethanol; Sapru et al. 1994). Perhaps more relevant to the present treatise, whereas acute ethanol activates adenylate cyclase, withdrawal from chronic ethanol decreases CREB phosphorylation in the amygdala and is linked to decrease in function of neuropeptide Y (NPY) and to the anxiety-like responses observed during acute ethanol withdrawal (Chance et al. 2000; Pandey 2004).
