Mouse parasubthalamic Crh neurons drive alcohol drinking escalation and behavioral disinhibition.

Autor: Kreifeldt M; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Okhuarobo A; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Dunning JL; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Lopez C; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Macedo G; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Sidhu H; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA., Contet C; The Scripps Research Institute, Department of Molecular Medicine, La Jolla, CA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 10. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1101/2024.07.06.602357
Abstrakt: Corticotropin-releasing factor (CRF, encoded by Crh ) signaling is thought to play a critical role in the development of excessive alcohol drinking and the emotional and physical pain associated with alcohol withdrawal. Here, we investigated the parasubthalamic nucleus (PSTN) as a potential source of CRF relevant to the control of alcohol consumption, affect, and nociception in mice. We identified PSTN Crh neurons as a neuronal subpopulation that exerts a potent and unique influence on behavior by promoting not only alcohol but also saccharin drinking, while PSTN neurons are otherwise known to suppress consummatory behaviors. Furthermore, PSTN Crh neurons are causally implicated in the escalation of alcohol and saccharin intake produced by chronic intermittent ethanol (CIE) vapor inhalation, a mouse model of alcohol use disorder. In contrast to our predictions, the ability of PSTN Crh neurons to increase alcohol drinking is not mediated by CRF 1 signaling. Moreover, the pattern of behavioral disinhibition and reduced nociception driven by their activation does not support a role of negative reinforcement as a motivational basis for the concomitant increase in alcohol drinking. Finally, silencing Crh expression in the PSTN slowed down the escalation of alcohol intake in mice exposed to CIE and accelerated their recovery from withdrawal-induced mechanical hyperalgesia. Altogether, our results suggest that PSTN Crh neurons may represent an important node in the brain circuitry linking alcohol use disorder with sweet liking and novelty seeking.
Competing Interests: Conflict of interest The authors have no competing financial interests to disclose.
Databáze: MEDLINE
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