mr-2266 and Hypoglycemia

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. Naloxone, a mu-opioid receptor antagonist and (5,7,8)-(+)-3,4-dichloro-N-methyl-N-(7,8,1-pyrrolidinyl)-1-oxaspirol+ ++ (4,5)dec-8-yl)-benzeneacetamide methanesulfonate, U-62,066E, a kappa-opioid receptor receptor agonist, showed neuroprotective actions against the hypoxia/hypoglycemia-induced deficit in glucose uptake. In contrast, morphine exhibited an exacerbating action. These results suggest that blockade of mu-opioid receptor- and stimulation of kappa-opioid receptor-mediated functions has a protective role against the hypoxia/hypoglycemia-induced decreases in glucose metabolism in hippocampal slices. Chronic administration of morphine (10 mg/kg) for 9 days affected neither the basal nor the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake. Rats treated with morphine chronically exhibited not only tolerance to the analgesic effect but also tolerance to the exacerbating action. However, chronic morphine did not modify U-62,066E-induced neuroprotection. These findings indicate that the receptor mechanisms of neuroprotection produced by the activation of kappa-opioid receptors may not be involved in mu-opioid receptor function.

Topics: Analgesics; Analgesics, Opioid; Animals; Benzomorphans; Brain Ischemia; Deoxyglucose; Drug Tolerance; Hippocampus; Hypoglycemia; Hypoxia, Brain; In Vitro Techniques; Male; Morphine; Naloxone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa