Delta-1 opioid receptor dependence of acute hypoxic adaptation

Previously an acute adaptation to hypoxia was induced by intermittent, severe hypoxia and this conditioned increase in survival time during subsequent hypoxia was blocked by naloxone. The current study further defined the opioid nature and the receptor type(s) involved in hypoxic adaptation by the use of (+)-naloxone (inactive isomer) and selective opioid antagonists. (+)-Naloxone failed to change significantly the survival times of hypoxic or sham conditioned mice during subsequent hypoxia. The selective opioid antagonists, 7-benzylidenenaltrexone, naltrindole, beta-funaltrexamine and norbinaltorphimine were administered subcutaneously before hypoxic or sham conditioning. The delta-1 and delta-2 selective antagonists, 7-benzylidenenaltrexone and naltrindole respectively, blocked the hypoxic conditioning-induced increase in survival time. The lowest effective 7-benzylidenenaltrexone dose was 3000-fold lower than the lowest effective naltrindole dose indicating that the acute adaptation to hypoxia was predominantly sensitive to delta-1 blockade. Neither the mu antagonist, beta-funaltrexamine, nor the kappa antagonist, norbinaltorphimine, significantly changed survival time in sham or hypoxic conditioned mice. These results support a delta-1 receptor mediated mechanism of acute adaptation to hypoxia.