Effects of naloxone, morphine and kappa-opioid receptor agonists on hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal slices from U-50,488H-tolerant rats.
The aim of the present study was to determine whether U-50,488H and U-62,066E, kappa-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a mu-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to kappa-opioid receptors does not affect the mu-opioid receptor-mediated neuroprotective or neurotoxic action.
Shibata
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Tominaga
K
K
Watanabe
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects*; D007003:Hypoglycemia; D000860:Hypoxia; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D011759:Pyrrolidines; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*
D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D003847:Deoxyglucose