| First Author | Torres Irizarry VC | Year | 2024 |
| Journal | Transl Psychiatry | Volume | 14 |
| Issue | 1 | Pages | 122 |
| PubMed ID | 38413577 | Mgi Jnum | J:348265 |
| Mgi Id | MGI:7609588 | Doi | 10.1038/s41398-024-02821-2 |
| Citation | Torres Irizarry VC, et al. (2024) Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice. Transl Psychiatry 14(1):122 |
| abstractText | Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HT(DRN)) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor alpha (ERalpha) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HT(DRN) neurons from naive male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HT(DRN) neurons from naive female mice. Notably, this higher sensitivity was blunted by 17beta-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERalpha and ERbeta are expressed in 5-HT(DRN) neurons, whereas ERalpha agonist depolarizes and ERbeta agonist hyperpolarizes 5-HT(DRN) neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HT(DRN) neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs' inhibitory effects on ethanol-induced burst firing of 5-HT(DRN) neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERalpha- or ERbeta-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERalpha/beta to prevent alcohol-induced activation of 5-HT(DRN) neurons, which in return leads to higher binge alcohol drinking. |
