{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:16Z","timestamp":1788419776674,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>GPR55 has attracted attention for its anti-inflammatory, neuroprotective, and neurotransmitter-modulating properties, suggesting a role in mood regulation. Here, we aimed to clarify the contribution of GPR55 to emotional responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female GPR55 knockout (GPR55KO) and wild-type (WT) C57BL\/6J mice were evaluated in the light-dark box, elevated plus maze, social interaction and tail suspension tests. Gene expression of the GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor \u03b12 and \u03b32 subunits was measured in the amygdala (AMY). A separate cohort underwent 30\u00a0min of restraint stress to assess hypothalamic-pituitary-adrenal (HPA) axis markers, including the expression of the Crf and Nrc3c1 genes in the paraventricular nucleus (PVN) and in the hippocampus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GPR55 deletion increased anxiety- and depressive-like behaviors across all the behavioral paradigms evaluated. GABA\n                      <jats:sub>A<\/jats:sub>\n                      \u03b1\n                      <jats:sub>2<\/jats:sub>\n                      gene expression in the AMY was elevated in GPR55KO mice of both sexes, while GABA\n                      <jats:sub>A<\/jats:sub>\n                      \u03b3\n                      <jats:sub>2<\/jats:sub>\n                      expression was not influenced by genotype. Restraint stress increased\n                      <jats:italic>Crf<\/jats:italic>\n                      and reduced\n                      <jats:italic>Nr3c1<\/jats:italic>\n                      similarly across genotypes. Notably, male GPR55KO mice displayed lower basal\n                      <jats:italic>Crf<\/jats:italic>\n                      levels than male controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Together, these findings indicate that loss of GPR55 heightens emotional vulnerability and alters specific GABAergic markers in the AMY while preserving HPA axis-related transcriptional response to acute stress. These results support GPR55 as a potential target for the modulation of anxiety- and depression-related states.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1766492","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:41:27Z","timestamp":1788417687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["GPR55 deletion increases anxiety- and depression-like behaviors and modifies amygdalar GABAA\u03b12 expression"],"prefix":"10.3389","volume":"17","author":[{"given":"Mar\u00eda S.","family":"Garc\u00eda-Guti\u00e9rrez","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC","place":["Alicante, Spain"]},{"name":"Red de Investigaci\u00f3n en Atenci\u00f3n Primaria de Adicciones, Instituto de Salud Carlos III, MICINN and FEDER","place":["Madrid, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL)","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Illescas","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC","place":["Alicante, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Gasparyan","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL)","place":["Alicante, Spain"]},{"name":"Hepatic and Intestinal Immunobiology Group, Dpto. 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