Mu but not delta opioid receptor stimulation intensifies kainic acid-induced neurotoxicity in rat hippocampus

In the present study, we compared the effects of the selective mu agonist, D-Ala2-N-methyl-pHe4-Gly-ol]-enkephalon (DAGO), and the selective delta agonist, D-Pen2,5]-enkephalin (DPDPE), on kainic acid-induced neurotoxicity in rats. Infusion of kainic acid (0.5 ug/1.5 ul, ic.v.) alone caused pyramidal cell loss predominantly in hippocampal field CA3 with minimal involvement of the CA1 field. Coadministration of DAGO plus kainic acid into the lateral ventricle intensified the extent of degeneration of hippocampal pyramidal cells in the CA1 field. The potentiating effect of DAGO was completely blocked by naltrexone. In contrast, DPDPE had no significant effect on kainic acid-induced neurotoxicity. Thus, activation of mu but not delta receptors intensifies the neurotoxic effects of kainic acid in the hippocampus.