Hyperglycaemia: a morphine-like effect produced by naloxone

1. Naloxone, which is often regarded as a pure opioid antagonist, produces effects similar to those produced by morphine. 2. In conscious rabbits implanted with an intracerebroventricular (i.c.v.) cannula, naloxone, whether given intravenously (1 mg/kg) or i.c.v. (1-100 microg), produced a significant rise in blood glucose levels. 3. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 microg, i.c.v.) was not influenced by the selective alpha1-adrenoceptor antagonist WB-4101 given either i.v. (50 microg) or i.c.v. (5 microg). 4. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 microg, i.c.v.) was completely blocked by pretreatment with the alpha2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v., or 100 microg, i.c.v.). However, hyperglycaemia to i.c.v. naloxone (100 microg) was not influenced by i.v. yohimbine (1 mg/kg). 5. Because naloxone behaves like morphine and produces hyperglycaemia in conscious rabbits, the drug may have an appreciable agonist activity and the hyperglycaemic response to naloxone is principally mediated via alpha2- but not alpha1-adrenoceptors.