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Leading hypotheses posit that once drug use becomes compulsive, DMS dependence degrades while DLS dependence increases. This shift may be mediated by changes in synaptic weights from glutamatergic inputs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Using a combination of western-blot, micro-injections, and ex-vivo electrophysiology in male and female C57BL\/6J mice, we investigated the role of \u03b1-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors AMPAR, which drive glutamatergic transmission, during quinine-adulterated alcohol drinking in the DMS and DLS across the development of aversion-resistant drinking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that AMPAR subunit composition and function change in the DMS across the development of aversion-resistant drinking whereby, calcium permeable (CP) - AMPARs drive behavior. Western blots revealed a negative relationship between DMS GluA1 and quinine-adulterated alcohol drinking in alcohol naive mice and a positive relationship between DMS Glu A1\/A2 ratios and quinine-adulterated alcohol drinking in aversion-resistant mice indicating that aversion-resistance positively predicts likelihood for CP-AMPAR expression in the DMS. Female aversion-resistant mice also had significant positive relationships with DMS or DLS Glu A1\/A2 ratios and female aversion-resistant mice had a significant negative relationship with GluA2 and aversion-resistant alcohol drinking. DMS CP-AMPAR antagonism caused an increase in quinine-adulterated alcohol drinking in alcohol na\u00efve mice suggesting that CP-AMPARs in the DMS prevent aversion-resistant drinking. Ex-vivo electrophysiology of DMS spiny projection neurons revealed that aversion-resistant drinking mice had greater inward rectification and CP-AMPAR antagonist sensitivity than alcohol na\u00efve mice indicating that spiny projection neurons in the DMS express more CP-AMPARs following the development of aversion-resistant drinking. However, sensitivity to CP-AMPAR antagonism negatively predicted aversion-resistant drinking in alcohol history mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data provide evidence that repeated alcohol binges alter DMS CP-AMPAR activity, where initial DMS activity acts to causally prevent aversion-resistant drinking but after repeated binges that result in aversion-resistant alcohol drinking, DMS spiny projection neurons recruit CP-AMPARs. CP-AMPAR antagonism was negatively association with aversion-resistant drinking within the alcohol history mice suggesting that plasticity of DMS CP-AMPARs is not related to quinine-sensitivity. These data provide evidence for a causal role of the DMS in aversion-resistant drinking and open questions as to the functional role of CP-AMPARs across the drinking history and striatal cell types.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07189-3","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:37:18Z","timestamp":1792388238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dorsomedial striatum calcium permeable AMPA receptors in the development of aversion-resistant alcohol drinking"],"prefix":"10.1007","author":[{"given":"Meredith R.","family":"Bauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Rangel-Barajas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"7189_CR1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013","unstructured":"American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. 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