The PreBötzinger Complex (preBC) Partially Mediates Opioid‐Induced Respiratory Depression in Young but not in Adult Rabbits

Abstract

It is yet unclear which brainstem areas are involved in respiratory depression by clinical doses of opioids. This study investigated whether the effects of the intravenous mu‐opioid agonist remifentanil could be reversed by local injection of naloxone (NAL) into the preBC and whether this reversal was different in young and adult animals.The study was approved by the local Animal Care Committee and conformed to NIH standards. 12 adult (3–4kg) and 15 young rabbits (13–23d, 110–550g) were anesthetized with 1–1.5 MAC sevoflurane, tracheotomized, ventilated and decerebrated. The location of the preBC was identified by neuronal recordings and the phrenic response to injection of D,L‐homocysteic acid. Remifentanil (0.08–0.5 mcg/kg/min) was infused intravenously until significant respiratory slowing and depression of peak phrenic activity (PPA) occurred. NAL (1mM, 70nl in young, 280nl in adults) was injected locally into the area of the preBC bilaterally. Local NAL partially reversed the depression of PPA (p=0.02) and the lengthening of expiratory time (p=0.01) in young but not in adult rabbits. Respiratory drive (PPA/inspiratory time) was unchanged. This is the first study to show that the preBC partially mediated the opioid‐induced changes in respiratory timing, though not in respiratory drive, in young rabbits but played no role in adult animals.Supported by FAER grant MRTG‐BS‐02/15/2010‐Stucke