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The aims of this mouse study were to improve understanding of these anxiolytic processes, determine whether there are corrective effects on reward processes, and provide further translational evidence for TRPC4\/C5 channel brain and neuron distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Mouse models of chronic social stress (CSS), with increased aversion and decreased reward responding, were applied to investigate the effects of a TRPC4\/TRPC5 channel inhibitor. RT\u2010qPCR and FISH were used to determine regional and neuronal gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Male mice underwent CSS, or were controls, and a TRPC4\/TRPC5 inhibitor or vehicle was administered prior to Pavlovian aversion learning: stressed\u2010vehicle mice displayed excessive Pavlovian learning, measured as high freezing to tone and context, and this was reduced by a TRPC4\/TRPC5 inhibitor. Different stressed and control mice were tested on discriminative reward learning: there was no TRPC4\/TRPC5 inhibitor effect on learning, but it did increase reward responding and effortful reward motivation in stressed mice. In naive male and female mice,\n                      <jats:italic>Trpc4<\/jats:italic>\n                      and\n                      <jats:italic>Trpc5<\/jats:italic>\n                      gene levels were moderate and high in glutamate principal neurons in basolateral amygdala and ventral hippocampus, respectively; co\u2010expression with the CCKB receptor was substantial.\n                      <jats:italic>TRPC4<\/jats:italic>\n                      and\n                      <jats:italic>TRP<\/jats:italic>\n                      <jats:italic>C5<\/jats:italic>\n                      were expressed by glutamate neurons in human amygdala and hippocampus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>This study furthers understanding of the therapeutic potential of TRPC4\/TRPC5 channel inhibition for excessive aversion processing and impaired reward processing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70305","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T01:13:15Z","timestamp":1766365995000},"page":"2139-2165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TRP canonical 4 and\/or 5 channel inhibition reduces aversion\u2010 and increases reward\u2010responding in chronically stressed mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Giulia","family":"Poggi","sequence":"first","affiliation":[{"name":"Preclinical Laboratory, Department of Adult Psychiatry and Psychotherapy University Hospital of Psychiatry and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Queisser","sequence":"additional","affiliation":[{"name":"Preclinical Laboratory, Department of Adult Psychiatry and Psychotherapy University 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