Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice
Open access copy at publisher website
Description
Alcohol-use-disorders are chronic relapsing illnesses, often co-morbid with anxiety. We have previously shown using the “drinking-in-the-dark” model in mice that the stimulation of the serotonin receptor 1A (5-HT1A) reduces ethanol binge-drinking behaviour and withdrawal-induced anxiety. The 5-HT1A receptor is located either on Raphe neurons as autoreceptors, or on target neurons as heteroreceptors. By combining a pharmacological approach with biased agonists targeting the 5-HT1A auto- or heteroreceptor and a chemogenetic approach (DREADDs), here we identified that ethanol-binge drinking behaviour is dependent on 5-HT1A autoreceptors and 5-HT neuronal function, with a transition from DRN-dependent regulation of short-term (6 weeks) ethanol intake, to MRN-dependent regulation after longer ethanol exposure (12 weeks). We further identified a serotonergic microcircuit (5-HTMRN→DG) originating from the MRN and projecting to the dentate gyrus (DG) of the hippocampus, that is specifically affected by, and modulates long-term ethanol consumption. The present study indicates that targeting Raphe nuclei 5-HT1A autoreceptors with agonists might represent an innovative pharmacotherapeutic strategy to combat alcohol abuse.
Impact and interest:
Citation counts are sourced monthly from Scopus and Web of Science® citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.
ID Code: | 237330 | ||||
---|---|---|---|---|---|
Item Type: | Contribution to Journal (Journal Article) | ||||
Refereed: | Yes | ||||
ORCID iD: |
|
||||
Additional Information: | Funding Information: This study was supported by Equipment, Pilot Data and Seed Grants from the Queensland University of Technology to Arnauld Belmer; and by the National Health and Medical Research Council (NHMRC) (GNT1146417) and the Edge Grant from the Queensland University of Technology to Selena E Bartlett. Open Access funding enabled and organized by CAUL and its Member Institutions. | ||||
Measurements or Duration: | 12 pages | ||||
DOI: | 10.1038/s41380-022-01789-z | ||||
ISSN: | 1359-4184 | ||||
Pure ID: | 122113265 | ||||
Divisions: | Current > QUT Faculties and Divisions > Faculty of Health Current > Schools > School of Clinical Sciences Current > Schools > School of Biomedical Sciences |
||||
Funding Information: | This study was supported by Equipment, Pilot Data and Seed Grants from the Queensland University of Technology to Arnauld Belmer; and by the National Health and Medical Research Council (NHMRC) (GNT1146417) and the Edge Grant from the Queensland University of Technology to Selena E Bartlett. Open Access funding enabled and organized by CAUL and its Member Institutions. | ||||
Funding: | |||||
Copyright Owner: | 2022 The Author(s) | ||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||
Deposited On: | 23 Jan 2023 06:38 | ||||
Last Modified: | 04 Aug 2024 16:40 |
Export: EndNote | Dublin Core | BibTeX
Repository Staff Only: item control page