The pontine respiratory group is involved in opioid‐induced respiratory depression in adult rabbits (712.6)

Abstract

Recent studies in adult dogs suggest that the parabrachial nucleus plays an important role in the respiratory depression by clinical concentrations of intravenous (IV) opioids (Prkic et al, 2012). This study investigated whether a similar area could be identified in adult rabbits. Each rabbit (2.2 ‐ 4.0 kg) was anesthetized with 1‐1.5 MAC sevoflurane, tracheotomized, ventilated and decerebrated. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 50 µM, 70 nl) was injected in a grid‐wise fashion from 1‐3 mm caudal of the inferior colliculi and 1‐4 mm lateral of midline into the dorso‐ventral center of neuronal activity. The area of maximal tachypnea as determined from the phrenic neurogram was on average 1.4 mm caudal to the inferior collicle, 2.4 mm lateral and 6.3 mm from the dorsal surface (n=5). Microinjection of the mu‐opioid agonist [D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin (DAMGO, 100 µM, 700 nl) into this region led to significant respiratory slowing without decrease in amplitude. Local injection of the opioid‐antagonist naloxone (1mM, 350 nl) partially reversed the respiratory depression caused by IV remifentanil (0.5 mcg/kg/min). These early studies suggest that lateral pontine mu‐opioid receptors in rabbits are responsible for bradypnea induced by systemically administered opioids at clinically relevant doses. Future studies will establish the magnitude of this effect.