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While increased glutamatergic input and decreased GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor sensitivity have been implicated, the impact of inhibitory signaling in VTA GABA neurons has not been fully addressed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>\n                      We used electrophysiological and ultrastructural approaches to assess the impact of chronic intermittent ethanol vapour exposure in mice on GABAergic transmission in VTA GABA neurons during withdrawal. We used CRISPR\/Cas9 ablation to mimic a somatodendritic adaptation involving the GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor (GABA\n                      <jats:sub>B<\/jats:sub>\n                      R) in ethanol\u2010na\u00efve mice to investigate its impact on anxiety\u2010related behaviour.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      The frequency of spontaneous inhibitory postsynaptic currents was reduced in VTA GABA neurons following chronic ethanol treatment and this was reversed by GABA\n                      <jats:sub>B<\/jats:sub>\n                      R inhibition, suggesting chronic ethanol strengthens the GABA\n                      <jats:sub>B<\/jats:sub>\n                      R\u2010dependent suppression of GABAergic input to VTA GABA neurons. Similarly, paired\u2010pulse depression of GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor\u2010dependent responses evoked by optogenetic stimulation of nucleus accumbens inputs from ethanol\u2010treated mice was reversed by GABA\n                      <jats:sub>B<\/jats:sub>\n                      R inhibition. Somatodendritic currents evoked in VTA GABA neurons by GABA\n                      <jats:sub>B<\/jats:sub>\n                      R activation were reduced following ethanol exposure, attributable to the suppression of GIRK (K\n                      <jats:sub>ir<\/jats:sub>\n                      3) channel activity. Mimicking this adaptation enhanced anxiety\u2010related behaviour in ethanol\u2010na\u00efve mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>Chronic ethanol weakens the GABAergic regulation of VTA GABA neurons in mice via pre\u2010 and postsynaptic mechanisms, likely contributing to their elevated activity during withdrawal and expression of anxiety\u2010related behaviour. As anxiety can promote relapse during abstinence, interventions targeting VTA GABA neuron excitability could represent new therapeutic strategies for treatment of alcohol use disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17335","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T01:48:38Z","timestamp":1727920118000},"page":"69-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chronic ethanol exposure in mice evokes pre\u2010 and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-9083","authenticated-orcid":false,"given":"Eric H.","family":"Mitten","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience University of Minnesota  Minneapolis Minnesota 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