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In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice
Author(s) -
Tree Keda C.,
Scotto di Perretolo Maud,
Peyronnet Julie,
Cayetanot Florence
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12588
Subject(s) - endocannabinoid system , cannabinoid , cannabinoid receptor , hyperventilation , endocrinology , hypoxia (environmental) , 2 arachidonoylglycerol , medicine , chemistry , receptor , agonist , organic chemistry , 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 ( CB 1 R ), participate in the modulation of respiration and its control. Blocking CB 1 Rs 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 CB 1 R s in normoxic and in hypoxic conditions. However, prenatal cannabis intoxication, caused by a daily injection of WIN 55,212‐2, 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 CB 1 Rs were blocked in WIN 55,212‐2 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 WIN 55,212‐2 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.