Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · May 2019
ReviewWiring the depressed brain: optogenetic and chemogenetic circuit interrogation in animal models of depression.
The advent of optogenetics and chemogenetics has revolutionized the study of neural circuit mechanisms of behavioral dysregulation in psychiatric disease. These powerful technologies allow manipulation of specific neurons to determine causal relationships between neuronal activity and behavior. ⋯ In comparison, chemogenetics have been relatively underutilized, despite offering unique advantages for probing long-term effects of manipulating neuronal activity. The ongoing development of optogenetic tools to probe in vivo function of ever-more specific circuits, combined with greater integration of chemogenetic tools and recent advances in vivo imaging techniques will continue to advance our understanding of the circuit mechanisms of depression.
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Neuropsychopharmacology · May 2019
Dynorphin-kappa opioid receptor activity in the central amygdala modulates binge-like alcohol drinking in mice.
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). ⋯ 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.