Sex‐ and age‐specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212‐2 in rats

Abstract

Background and Purpose: Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited.Experimental Approach: We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212-2 [WIN], 0.5 mgÁkg À1 Áday À1 ) on the respiratory control system in neonatal (P0, P6-7 and P12-13) and juvenile (P27-28) male and female rats.Key Results: WIN administration to pregnant rats interfered sex-specifically with breathing regulation of offspring, promoting a greater sensitivity to CO 2 at all ages in males (except P6-7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6-7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB 1 ) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5-HT) neurons in the raphe magnus nucleus of P0 females.Conclusions and Implications: These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex-specific consequences for the respiratory control system.

Exercise derived myokine irisin as mediator of cardiorespiratory, metabolic and thermal adjustments during central and peripheral chemoreflex activation

“…The indirect calorimetry method by measuring O 2 consumption (VO 2 ) with flow- through push mode configuration in an open respirometry system was used for metabolic rate inference 35 , 36 . The chamber air flow (2.2 L/min −1 ) was maintained through an aquarium pump that directed the air to the chamber entrance when the animals were exposed to ambient air and by gas mixture cylinders coupled to a flowmeter (model 822-13-OV1-PV2-V4, Sierra Instruments, Monterey, CA) when exposed to hypercapnia or hypoxia.…”