J.P. and F.C. contributed equally to this work.
In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice
Article first published online: 10 APR 2014
© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience
Volume 40, Issue 1, pages 2196–2204, July 2014
How to Cite
Tree, K. C., Scotto di Perretolo, M., Peyronnet, J. and Cayetanot, F. (2014), In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice. European Journal of Neuroscience, 40: 2196–2204. doi: 10.1111/ejn.12588
- Issue published online: 6 JUL 2014
- Article first published online: 10 APR 2014
- Manuscript Accepted: 13 MAR 2014
- Manuscript Revised: 21 JAN 2014
- Manuscript Received: 22 AUG 2013
- lack of oxygen;
Cannabis is one of the most commonly used recreational drugs at ages highly correlated with potential pregnancy. Endocannabinoid signalling regulates important stages of neuronal development. When cannabinoid receptors, which are widely distributed through the nervous system, are activated by exogenous cannabinoids, breathing in adult rats is depressed. Here, we show that, in newborn mice, endocannabinoids, through the activation of cannabinoid receptor type 1 (CB1R), participate in the modulation of respiration and its control. Blocking CB1Rs at birth suppressed the brake exerted by endocannabinoids on ventilation in basal and in hypoxic conditions. The number of apnoeas and their duration were also minimized by activation of CB1Rs in normoxic and in hypoxic conditions. However, prenatal cannabis intoxication, caused by a daily injection of WIN55,212-2, in pregnant mice durably modified respiration of the offspring, as shown by hyperventilation in basal conditions, an altered chemoreflex in response to hypoxia, and longer apnoeas. When CB1Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment.