The rewarding and anxiolytic properties of ethanol within the central nucleus of the amygdala: Mediated by genetic background and nociceptin but not the CRF1 receptor.

In humans, alcohol is consumed for its rewarding and anxiolytic effects. The Central Nucleus of the Amygdala (CeA) is considered a neuronal nexus that regulates fear, anxiety and drug self-administration. Manipulations of the CeA alter ethanol (EtOH) consumption under numerous EtOH self-administration models. The experiments determined if EtOH is reinforcing/anxiolytic within the CeA, if selective breeding for high alcohol consumption alters the rewarding properties of EtOH in the CeA, and if the reinforcing/anxiolytic effects of EtOH in the CeA are mediated by the neuropeptides corticotropin-releasing factor (CRF) and nociceptin. The reinforcing properties of EtOH were determined by having male Wistar and Taconic Alcohol-Preferring (tP) rats self-administer EtOH directly into the CeA. The expression of anxiety-like behaviors was assessed through multiple behavioral models (social interaction, acoustic startle, open field). Co-administration of EtOH and a CRF1 antagonist (NBI 35965) or nociceptin on self-administration into the CeA and anxiety-like behaviors was determined. EtOH was self-administered directly into the lateral CeA and tP rats self-administered a lower concentration of EtOH than Wistar rats. EtOH microinjected into the lateral CeA reduced the expression of anxiety-like behaviors, indicating an anxiolytic effect. The co-administration of NBI 35965 failed to alter the rewarding/anxiolytic properties of EtOH in the CeA. In contrast, co-administration of the nociceptin enhanced both EtOH reward and anxiolysis in the CeA. The data indicate that the lateral CeA is a key anatomical location that mediates the rewarding and anxiolytic effects of EtOH and activation of nociceptin receptors augment the effects of EtOH in this region. SIGNIFICANCE STATEMENT: Alcohol is consumed for the stimulatory, rewarding, and anxiolytic properties of the drug of abuse. The current data are the first to establish that alcohol is reinforcing and anxiolytic within the lateral central nucleus of the amygdala (CeA), and that the Nociceptin system regulates these effects of alcohol within the CeA.