Differential effects of mu and kappa opioid analgesics on cerebral glucose utilization in the rat

The autoradiographic 2-deoxy-D-[1-(-14)C]glucose ([14C]2-DG) method was used to map the effects of subcutaneous (s.c.) morphine (8.0 mg/kg), oxymorphone (0.4 mg/kg) and nalbuphine (16.0 mg/kg) on local cerebral glucose utilization (LCGU), an index of local brain function. At the dosages administered, effects of the opioid agonists on LCGU were very restricted. The mu agonists, injected 15 min before [14C]2-DG, decreased LCGU in thalamic nuclei, including some of those which have been implicated in somatosensory processing, and in the dorsal tegmental nucleus. Nalbuphine did not produce these effects, but stimulated LCGU in nuclei of the spinal tract of the trigeminal nerve and in the globus pallidus. All of the effects on LCGU were blocked by prior administration of naloxone (1.0 or 10.0 mg/kg, s.c., 5 min before morphine or nalbuphine, respectively). Our findings suggest that different supraspinal mechanisms are involved in the actions of mu vs kappa opioids, and indicate that the [14C]2-DG procedure might be helpful in elucidating the anatomical areas involved.