%0 Journal Article
%T Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment
%A Francesca R D¡¯Amato
%A Karine Bachand
%A Marco Battaglia
%A Orlane Rossignol
%A Yves De Koninck
%J Journal of Psychopharmacology
%@ 1461-7285
%D 2019
%R 10.1177/0269881118784872
%X 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. We hypothesized that the acid-sensing ion channel inhibitor amiloride can modulate repeated cross-fostering animals¡¯ exaggerated responses to carbon dioxide and nociceptive thermal stimulation. 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. 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¡Árepeated cross-fostering interaction. In contrast, repeated cross-fostering animals¡¯ 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¡Áamiloride interaction. Single-dose nebulized amiloride decreased repeated cross-fostering animals¡¯ 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
%K Neurophysiology
%K health sciences
%K pain
%K biomarkers
%U https://journals.sagepub.com/doi/full/10.1177/0269881118784872