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.
Lason
W
W
Department of Anatomy and Biology, School of Medicine, East Carolina University, Greenville, NC 27858-4354.
Simpson
J N
JN
McGinty
J F
JF
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012640:Seizures / Q000139:chemically induced
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; D007608:Kainic Acid