Dexamethasone blocking effects on mu- and delta-opioid-induced seizures involves kappa-opioid activity in the rabbit

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 [D-Ala(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 pre-treatment prevented DAMGO-, deltorphin II- and beta-endorphin-induced seizures as well as changes in background EEG, physical parameters and overt behaviour induced by mu-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.