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 mug), produced a significant rise in blood glucose levels. 3. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 mug, i.c.v,) was not influenced by the selective alpha (1)-adrenoceptor antagonist WB-4101 given either i.v. (50 mug) or i.c.v. (5 mug). 4. Hyperglycaemia in response to naloxone (1 mg/kg, i.v., or 100 mug, i.c.v.) was completely blocked by pretreatment with the alpha (2)-adrenoceptor antagonist yohimbine (1 mg/kg, i.v., or 100 mug, i.c.v.). However, hyperglycaemia to i.c.v, naloxone (100 mug) 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 alpha (2)- but not alpha (1)-adrenoceptors.