Abstract
Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling in escalated alcohol consumption associated with dependence and stress exposure, involvement of the dynorphin/kappa opioid receptor (DYN/KOR) system in binge-like drinking has not been fully explored. Here we used pharmacological and chemogenetic approaches to examine the influence of DYN/KOR signaling on alcohol consumption in the drinking-in-the-dark (DID) model of binge-like drinking. Systemic administration of the KOR agonist U50,488 increased binge-like drinking (Experiment 1) while, conversely, systemic administration of the KOR antagonist nor-BNI reduced drinking in the DID model (Experiment 2). These effects of systemic KOR manipulation were selective for alcohol as neither drug influenced consumption of sucrose in the DID paradigm (Experiment 3). In Experiment 4, administration of the long-acting KOR antagonist nor-BNI into the central nucleus of the amygdala (CeA) decreased alcohol intake. Next, targeted “silencing” of DYN+ neurons in the CeA was accomplished using a chemogenetic strategy. Cre-dependent viral expression in DYN+ neurons was confirmed in CeA of Pdyn-IRES-Cre mice and functionality of an inhibitory (hM4Di) DREADD was validated (Experiment 5). Activating the inhibitory DREADD by CNO injection reduced binge-like alcohol drinking, but CNO injection did not alter alcohol intake in mice that were treated with control virus (Experiment 6). Collectively, these results demonstrate that DYN/KOR signaling in the CeA contributes to excessive alcohol consumption in a binge-drinking model.
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This work was supported by NIH grants P50 AA10716 (HCB), U01 AA014095 (HCB, MFL, WCG HLH), F32 AA023700 (RIA), T32 AA007474 (RIA), U01 AA020911 (TLK), U24 AA025475 (TLK), P60 AA011605 (TLK), and F31 AA025835 (DB), and VA grant BX000813 (HCB).
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Anderson, R.I., Lopez, M.F., Griffin, W.C. et al. Dynorphin-kappa opioid receptor activity in the central amygdala modulates binge-like alcohol drinking in mice. Neuropsychopharmacol. 44, 1084–1092 (2019). https://doi.org/10.1038/s41386-018-0294-3
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DOI: https://doi.org/10.1038/s41386-018-0294-3
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