Chunk #43 — 3 Neural Substrates for the Negative Emotional State Associated with Alcoholism — 3.2 Between-System Neuroadaptations that Contribute to Compulsivity Associated with the Dark Side of Alcoholism
Although less well developed, evidence supports a role of norepinephrine systems in the extended amygdala in the negative motivational state and increased self-administration associated with dependence. Substantial evidence has accumulated suggesting that in animals and humans, central noradrenergic systems are activated during acute withdrawal from ethanol. Alcohol withdrawal in humans is associated with activation of noradrenergic function, and the signs and symptoms of alcohol withdrawal in humans are blocked by postsynaptic β-adrenergic blockade (Romach and Sellers 1991). Alcohol withdrawal signs are also blocked in animals by administration of α1 antagonists and β-adrenergic antagonists and selective blockade of norepinephrine synthesis (Trzaskowska and Kostowski 1983). In dependent rats, the α1, antagonist prazosin selectively blocked the increased drinking associated with acute withdrawal (Walker et al. 2008). Thus, converging data suggest that noradrenergic neurotransmission is enhanced during ethanol withdrawal and that noradrenergic functional antagonists can block aspects of ethanol withdrawal.
