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bioRxiv · 10.1101/2020.02.07.939496

Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcoholdependence

Kreifeldt, M.·Herman, M. A.·Sidhu, H.·de Macedo, G. C.·Shahryari, R.·Roberto, M.·Contet, C.
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Abstract

BackgroundCorticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking. However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement. MethodsWe tested this hypothesis in male mice and used chemogenetics to stimulate CeA CRF neurons in vitro and in vivo. ResultsWe first observed that Crh mRNA expression in the anterior part of the mouse CeA, at the junction with the interstitial nucleus of the posterior limb of the anterior commissure, correlates positively with alcohol intake in C57BL/6J males with a history of chronic binge drinking. We then found that chemogenetic activation of CeA CRF neurons in Crh-IRES-Cre mouse brain slices increases gamma-aminobutyric acid (GABA) release in the medial CeA in part via CRF1 receptor activation, indicating local CRF release. While chemogenetic stimulation of CeA CRF neurons exacerbated novelty-induced feeding suppression, as seen in C57BL/6J males withdrawn from chronic intermittent alcohol inhalation, it had no effect on voluntary alcohol consumption, following either acute or chronic manipulation. ConclusionsAltogether, these findings indicate that hyperactivity of CeA CRF neurons may contribute to elevated CeA GABA levels and negative affect during alcohol withdrawal but is not sufficient to drive alcohol intake escalation in dependent mice.

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Kreifeldt, M., Herman, M. A., Sidhu, H., de Macedo, G. C., Shahryari, R., Roberto, M., Contet, C.. 2020-02-09. Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcoholdependence. https://doi.org/10.1101/2020.02.07.939496

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