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The Role of the Central Amygdala in Alcohol Dependence
Marisa Roberto1, Dean Kirson1, Sophia Khom1
1Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central nucleus of the amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptive mechanisms associated with alcohol dependence. Acute alcohol facilitates γ-aminobutyric acid (GABA)ergic transmission in the CeA via both pre- and postsynaptic mechanisms, and chronic alcohol increases baseline GABAergic transmission. Acute alcohol inhibits glutamatergic transmission via effects at N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the CeA, whereas chronic alcohol up-regulates NMDA receptor (NMDAR)-mediated transmission. Pro- (e.g., corticotropin-releasing factor [CRF]) and antistress (e.g., nociceptin/orphanin FQ, oxytocin) neuropeptides affect alcohol- and anxiety-related behaviors, and also alter the alcohol-induced effects on CeA neurotransmission. Alcohol dependence produces plasticity in these neuropeptide systems, reflecting a recruitment of those systems during the transition to alcohol dependence.
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