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  • Title: Central nucleus of the amygdala projections onto the nucleus accumbens core regulate binge-like alcohol drinking in a CRF-dependent manner.
    Author: Borrego MB, Grigsby KB, Townsley KG, Chan A, Firsick EJ, Tran A, Savarese A, Ozburn AR.
    Journal: Neuropharmacology; 2022 Feb 01; 203():108874. PubMed ID: 34748860.
    Abstract:
    RATIONALE: The nucleus accumbens (NAc) is important for regulating a number of behaviors, including alcohol and substance use. We previously found that chemogenetically manipulating neuronal activity in the NAc core regulates binge-like drinking in mice. The central amygdala (CeA) is also an important regulator of alcohol drinking, and projects to the NAc core. We tested whether neuronal projections from the CeA to the NAc core, or neuropeptides released by the CeA in the NAc core, could regulate binge drinking. METHODS: For experiment 1, mice were administered AAV2 Cre-GFP into the NAc core and a Cre-inducible DREADD [AAV2 DIO- hM3Dq, -hM4Di, or -mCherry control] into the CeA. We tested the effects of altering CeA to NAc core activity on binge-like ethanol intake (via "Drinking in the Dark", DID). For experiment 2, we bilaterally microinfused corticotropin releasing factor (CRF), neuropeptide Y (NPY), or somatostatin (SST) into the NAc core prior to DID. For experiment 3, we tested whether intra-NAc CRF antagonism prevented reductions in drinking induced by CNO/hM3Dq stimulation of CeA->NAc projections. RESULTS: Chemogenetically increasing activity in neurons projecting from the CeA to NAc core decreased binge-like ethanol drinking (p < 0.01). Intra-NAc core CRF mimicked chemogenetic stimulation of this pathway (p < 0.05). Binge-like drinking was unaffected by the doses of NPY and SST tested. Lastly, we found that intra-NAc CRF antagonism prevented reductions in drinking induced by chemogenetic stimulation of CeA->NAc projections. These findings demonstrate that neurons projecting from the CeA to NAc core that release CRF are capable of regulating binge-like drinking in mice.
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