The role of opioid receptors in hypoxic preconditioning against seizures in brain

Preconditioning is defined as an adaptive mechanism produced by short perio ds of hypoxia/ischemia, resulting in protection against subsequent ischemic insult and development of seizures. Results of the present study demonstra te that an episode of normobar hypoxia reduces the susceptibility to convul sions induced by pentylenetetrazol (PTZ) 30 min, 24 h, as well as 4 and 7 d ays later. Administration of morphine showed similar effects after 24 h. Na loxone, given before ischemic preconditioning, as well as morphine, blocked the development of the protection. Administration of D-Ala-Met-enkephalin -Gly- ol (DAMGO - a selective mu - opioid receptor agonist), as well as tra ns-3,4-dichloro -N-methyl-N- [7-(1-pyrrolidinyl) cycloexilbenzeneacetamide ethane sulfonate] (U-69,593 - a selective kappa-opioid receptor agonist), m imicked the effects of hypoxic preconditioning (HPC). ( -)-N- (Cyclopropylm ethyl) -4,14- dimethoxymorphinan- 6-one (cyprodime - a selective mu-opioid receptor antagonist, as well as nor-binaltorphimine dihydrochloride (nor-BN I - selective kappaopioid receptors antagonist), given before HPC as well a s before respective opioid receptor agonists, blocked the development of th e protection. This study provides evidence that mu- and kappa-opioid recept ors are involved in HPC against seizures in the brain. (C) 2000 Elsevier Sc ience Inc. All rights reserved.