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.

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Fig. 1: The molecular phenotype of CeA CART cells.
Fig. 2: Yohimbine-induced reinstatement of alcohol seeking activates CART neurons within the CeA.
Fig. 3: CART signalling within the CeA in necessary, but not sufficient for reinstatement of alcohol seeking.
Fig. 4: CeA CART signalling does not alter the motivation to consume alcohol.
Fig. 5: CeA CART signalling mediates anxiety-like behaviour following alcohol consumption.


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LCW, AH, BL, KH & EJC conducted experiments, LCW and AH performed analysis. LCW & AJL conceived experiments and wrote the paper with input from all authors.

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Correspondence to Leigh C. Walker or Andrew J. Lawrence.

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Walker, L.C., Hand, L.J., Letherby, B. et al. Cocaine and amphetamine regulated transcript (CART) signalling in the central nucleus of the amygdala modulates stress-induced alcohol seeking. Neuropsychopharmacol. (2020).

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