Chunk #30 — 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
Within-system neuroadaptations to chronic drug exposure include decreases in function of the same neurotransmitter systems in the same neurocircuits implicated in the acute reinforcing effects of drugs of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal and protracted abstinence. This decrease in dopamine function is hypothesized to lead to decreased motivation for non-drug-related stimuli and increased sensitivity to the abused drug (Melis et al. 2005). Activation of the mesolimbic dopamine system has long been known to be critical for the acute rewarding properties of psychostimulant drugs and to be associated with the acute reinforcing effects of alcohol (Koob 1992; McBride and Li 1998; Nestler 2005). However, the magnitude of the increase in dopaminergic activity produced by alcohol pales in comparison to that of psychostimulant “intoxication.” For example, intravenous cocaine self-administration produces a 200% increase in extracellular dopamine (Weiss et al. 1992b) compared with ethanol which produces a 20% increase in extracellular dopamine in the nucleus accumbens (Doyon et al. 2003) and heroin (which does not increase extracellular dopamine
