Intertrigeminal region attenuates reflex apnea and stabilizes respiratory pattern in rats

The goal of the present study was to determine whether the newly described anatomical pathway involving the pontine intertrigeminal region (ITR), (Chamberlin and Saper, 1998), has a physiological role in mediating or modulating vagally-induced reflex apnea. We explored the ITR impact on vagal reflex apnea elicited by intravenuously injected 5-HT in ten anesthetized rats. The animals had a catheter inserted into the femoral vein for administration of 5-HT (0.00375 mg) and respiration was recorded by piezo-electric crystal. Multibarrel pipettes were used to pressure inject glutamate (5–10 nl, 10 mM), kynurenic acid (10 nl, 50 mM, a glutamate receptor antagonist), and red dye into the ITR, unilaterally and bilaterally. Intravenous administration of 5-HT produced an immediate 3-s apnea. Microinjections of glutamate into the ITR produced apneas, while microinjections of kynurenic acid blocked the glutamate effect. Following glutamate antagonism, subsequent administration of 5-HT produced apneas of much longer duration (8 s). Acute ponto-medullary transection in two animals yielded even greater prolongation of 5-HT-induced apnea. We conclude that a physiological role for the ITR in respiration is to attenuate vagally-induced reflex apneas. This finding is in agreement with the general modulatory role of pontine structures in autonomic activities including respiration, heart rate and regulation of blood pressure. In addition, our data indicate that medullary circuits, independent of pontine structures, are sufficient to produce 5-HT induced reflex apnea.