Cannabinoid Receptor mRNA Expression in Central and Peripheral Tissues in a Rodent Model of Peritonitis.

Our laboratory investigates changes in the respiratory pattern during systemic inflammation in various rodent models. The endogenous cannabinoid system (ECS) regulates cytokine production and mitigates inflammation. Inflammation not only affects cannabinoid (CB) 1 and CB2 receptor gene expression ( and ), but also increases the predictability of the ventilatory pattern. Our primary objective was to track ventilatory pattern variability and transcription of and , and of , , and tumor necrosis factor-alpha ( mRNAs at multiple time points in central and peripheral tissues during systemic inflammation induced by peritonitis. In male Sprague Dawley rats (=24), we caused peritonitis by implanting a fibrin clot containing either 0 or 25×10 intraperitoneally. We recorded breathing with whole-animal plethysmography at baseline and 1 h before euthanasia. We euthanized the rats at 3, 6, or 12 h after inoculation and harvested the pons, medulla, lung, and heart for gene expression analysis. With peritonitis, more than was correlated to , , and mRNAs in medulla, pons, and lung and changed oppositely in the pons, medulla, and lung. These changes were associated with increased predictability of ventilatory pattern. Specifically, nonlinear complexity index correlated with increased mRNA in the pons and medulla, and coefficient of variation for cycle duration correlated with and mRNAs in the lung. The mRNAs for ECS receptors varied with time during the central and peripheral inflammatory response to peritonitis. These changes occurred in the brainstem, which contains the network that generates breathing pattern and thus, may participate in ventilatory pattern changes during systemic inflammation.