KAPPA-OPIOID RECEPTOR AGONIST PROTECTS AGAINST ISCHEMIC REDUCTION OF 2-DEOXYGLUCOSE UPTAKE IN MORPHINE-TOLERANT RATS

We examined the effects of mu-opioid receptor agonist and antagonists, and kappa-opioid receptor agonist on the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake of rat hippocampal slices. Naloxon e, a mu-opioid receptor antagonist and lidinyl)-1-oxaspirol{4,5}dec-8- yl)-benzeneacetamid methanesulfonate, U-62,066E, a kappa-opioid recept or agonist, showed neuroprotective actions against the hypoxia/hypogly cemia-induced deficit in glucose uptake. In contrast, morphine exhibit ed an exacerbating action. These results suggest that blockade of mu-o pioid receptor- and stimulation of kappa-opioid receptor-mediated func tions has a protective role against the hypoxia/hypoglycemia-induced d ecreases in glucose metabolism in hippocampal slices. Chronic administ ration of morphine (10 mg/kg) for 9 days affected neither the basal no r the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake. Rats treated with morphine chronically exhibited not only tolerance t o the analgesic effect but also tolerance to the exacerbating action. However, chronic morphine did not modify U-62,066E-induced neuroprotec tion. These findings indicate that the receptor mechanisms of neuropro tection produced by the activation of kappa-opioid receptors may not b e involved in mu-opioid receptor function.