Negative feedback regulation of alcohol ingestion through the FGF21-PVH oxytocin-VTA dopamine system.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41533444.
- Also identified by DOI 10.1073/pnas.2525172122 and PMC identifier 12818416.
- Licence recorded as CC BY-NC-ND.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Alcohol has a notable negative impact on global health. Understanding its physiological regulation is crucial to addressing alcohol use. Here, we show that FGF21-oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVH<sup>OXT</sup>)-dopamine neurons in the ventral tegmental area (VTA<sup>DA</sup>) negatively regulate the drive to drink alcohol. Alcohol induces FGF21 signaling, which activates PVH<sup>OXT</sup> and induces oxytocin release in the VTA. The VTA<sup>DA</sup> neurons are activated hours after alcohol ingestion, which reduces the drive to drink alcohol, extends the interdrink interval, and thereby reduces alcohol consumption. The system is downregulated in a mouse model of alcohol dependence, and activating the system with FGF21-inducing sugars reduces alcohol ingestion and prevents binge drinking and alcohol dependence. Therefore, FGF21-inducing nutraceuticals can substitute for alcohol by supplementing the FGF21-PVH<sup>OXT</sup>-VTA<sup>DA</sup> negative feedback signal to attenuate alcohol-related behaviors in mice.
Medical subject headings
- Fibroblast Growth Factors
- Oxytocin
- Ventral Tegmental Area
- Paraventricular Hypothalamic Nucleus
- Dopaminergic Neurons
- Alcohol Drinking
- Ethanol