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.