A balancing act: the role of pro‐ and anti‐stress peptides within the central amygdala in anxiety and alcohol use disorders

The central nucleus of the amygdala (CeA) is widely implicated as a structure that integrates both appetitive and aversive stimuli. While intrinsic CeA microcircuits primarily consist of GABAergic neurons that regulate amygdala output, a notable feature of the CeA is the heterogeneity of neuropeptides and neuropeptide/neuromodulator receptors that it expresses. There is growing interest in the role of the CeA in mediating psychopathologies, including stress and anxiety states and their interactions with alcohol use disorders. Within the CeA, neuropeptides and neuromodulators often exert pro‐ or anti‐ stress actions, which can influence anxiety and alcohol associated behaviours. In turn, alcohol use can cause adaptions within the CeA, which may render an individual more vulnerable to stress which is a major trigger of relapse to alcohol seeking. This review examines the neurocircuitry, neurochemical phenotypes and how pro‐ and anti‐stress peptide systems act within the CeA to regulate anxiety and alcohol seeking, focusing on preclinical observations from animal models. Furthermore, literature exploring the targeting of genetically defined populations or neuronal ensembles and the role of the CeA in mediating sex differences in stress x alcohol interactions are explored.