{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:42:59Z","timestamp":1780555379901,"version":"3.54.1"},"reference-count":59,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T00:00:00Z","timestamp":1530576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2016-06145"],"award-info":[{"award-number":["RGPIN-2016-06145"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Early life adversities are risk factors for anxiety disorders and for pain syndromes, which are, in turn, highly comorbid with anxiety disorders. Repeated cross-fostering mouse pups to adoptive lactating females induces epigenetic modification and heightened mRNA-expression of the acid-sensing-ion-channel-1 gene, altered nociception, and hypersensitivity to 6% carbon dioxide air mixtures, a trait marker of specific human anxiety disorders such as, most clearly and prominently, panic disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>We hypothesized that the acid-sensing ion channel inhibitor amiloride can modulate repeated cross-fostering animals\u2019 exaggerated responses to carbon dioxide and nociceptive thermal stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Respiratory carbon dioxide sensitivity was assessed by plethysmography during 6% carbon dioxide air mixture challenges, and nociception was assessed by latency of paw withdrawal to thermal stimulation, in repeated cross-fostering and control animals. To circumvent the blood-brain barrier, prior to testing, amiloride was nebulized in a plethysmograph. Data were analyzed by general linear models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Analyses of tidal volume responses to 6% carbon dioxide of animals pre-treated with nebulized amiloride\/saline in a randomized crossover design showed significant modulatory effect of amiloride, and amiloride\u00d7repeated cross-fostering interaction. In contrast, repeated cross-fostering animals\u2019 responses to 6% carbon dioxide after intraperitoneal amiloride, saline, or no treatment, were no different. Analyses of responses to thermal stimuli showed a significant modulatory effect of nebulized amiloride, and repeated cross-fostering\u00d7amiloride interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Single-dose nebulized amiloride decreased repeated cross-fostering animals\u2019 carbon dioxide sensitivity and nociception indices to levels that were no different from those of control animals. Inasmuch as these results pertain to human anxiety and\/or pain hypersensitivity, our findings provide a rationale for studying inhaled amiloride in some anxiety disorders and\/or pain syndromes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0269881118784872","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T06:27:53Z","timestamp":1530599273000},"page":"101-108","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment"],"prefix":"10.1177","volume":"33","author":[{"given":"Marco","family":"Battaglia","sequence":"first","affiliation":[{"name":"Child Youth and Emerging Adult Programme, Centre for Addiction & Mental Health, Toronto, ON, Canada"},{"name":"Department of Psychiatry and Neuroscience, Universit\u00e9 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