Previous data indicate that intracerebroventricular administration of agonists for mu- and delta -opioid receptors induces limbic seizures in rats, but no data are reported in rabbits. We found that the mu- and delta -opioid peptides [DAla(2)-N,Me-Phe(4)-Gly(5)-ol]enkephalin (DAMGO), beta -endorphin and deltorphin II, induced EEG non-convulsive hippocampal seizures, and changes in hippocampal background EEG, physical parameters and overt behaviour after central administration. Dexamethasone pretreatment prevented DAMGO-, deltorphin II- and beta -endorphin-induced seizures as well as changes in background EEG, physical parameters and overt behaviour induced by CI-opioid agonists, Dexamethasone antagonism on opioid action was blocked by pre-treatment with a protein synthesis inhibitor, cycloheximide or by the kappa -opioid antagonist nor-binaltorphimine. Our data suggest that dexamethasone influences opioid actions at mu- and delta -receptors via a protein synthesis mechanism involving kappa -opioid receptors, Copyright (C) 2001 S. Karger AG. Basel.