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Group II metabotropic glutamate receptors (mGlu2\/3) act primarily as presynaptic autoreceptors that regulate glutamate release. However, how voluntary alcohol intake alters mGlu2\/3 expression within reward circuitry remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>We examined mGlu2\/3 protein expression following a history of voluntary ethanol exposure and operant self\u2010administration and, in separate cohorts, assessed the functional impact of group II receptor modulation on binge\u2010like ethanol intake. Male C57BL\/6J mice received two weeks of home\u2010cage access to sweetened ethanol or sucrose followed by 35\u2009days of operant self\u2010administration. Immediately after the final session, tissue punches from the nucleus accumbens (NAc), amygdala, and prefrontal cortex were collected for immunoblot analysis. mGlu2\/3 expression was reduced in the NAc of ethanol\u2010exposed mice with no statistically significant changes detected in the amygdala or prefrontal cortex. In separate binge\u2010drinking cohorts, systemic administration of the mGlu2\/3 agonist LY379268 reduced binge\u2010like ethanol intake in a limited\u2010access home\u2010cage drinking model, whereas positive allosteric modulation of mGlu2 receptors with LY487379 was ineffective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Voluntary ethanol self\u2010administration was associated with reduced mGlu2\/3 protein expression in the NAc. Systemic pharmacological activation of group II receptors suppressed binge\u2010like ethanol consumption. These findings identify mGlu2\/3 dysregulation in a key reward\u2010related brain region as a molecular adaptation associated with voluntary ethanol intake and demonstrate mechanistic regulation of binge drinking. This suggests that group II metabotropic glutamate signaling is a viable therapeutic target for treating AUD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70409","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T04:20:55Z","timestamp":1788754855000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ethanol Self\u2010Administration Reduces\n                    <scp>mGlu2<\/scp>\n                    \/3 Protein Expression in the Nucleus Accumbens and\n                    <scp>mGlu2<\/scp>\n                    \/3 Activation Suppresses Binge Drinking in Male Mice"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9119-7212","authenticated-orcid":false,"given":"Cassandra G.","family":"Modrak","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies School of Medicine, The University of North Carolina at Chapel 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