Cocaine and amphetamine regulated transcript (CART) signalling in the central nucleus of the amygdala modulates stress-induced alcohol seeking

The central nucleus of the amygdala (CeA) is a key hub of the neural circuitry regulating alcohol and stress interactions. However, the exact neuronal populations that govern this interaction are not well defined. Here we examined the role of the neuropeptide cocaine and amphetamine regulated transcript (CART) within the CeA in stress-induced alcohol seeking. We found that CART-containing neurons are predominantly expressed in the capsular/lateral division of the CeA and are a subpopulation of protein kinase Cδ (PKCδ) cells, distinct from corticotrophin releasing factor (CRF)-expressing cells. Both stress (yohimbine) and stress-induced alcohol seeking activated CART cells within the CeA, while neutralisation of endogenous CeA CART signalling (via antibody administration) attenuated stress-induced alcohol, but not sucrose seeking. Further, blocking CART signalling within the CeA did not alter the motivation to obtain and consume alcohol but did attenuate stressor-induced anxiety-like behaviour during abstinence from alcohol. Together, these data identify CeA CART cells as a subpopulation of PKCδ cells that influence stress × alcohol interactions and mediate stress-induced alcohol seeking behaviours.