Glucose utilization in the rat brain during chronic morphine treatment and naloxone-precipitated morphine withdrawal

Rates of local cerebral glucose utilization (LCGU) were measured in morphine-dependent and morphine-abstinent rats. Morphine pellets were implanted s.c. (one pellet 7 days before glucose utilization measurement and two pellets 4 days before the measurement) to produce opioid dependence. LCGU rates in 85 brain regions of placebo- and morphine-pelleted rats were similar. In contrast, LCGU rates, 5 hr after implantation of one morphine pellet, were decreased significantly in six areas. The lack of a chronic morphine effect on LCGU suggests tolerance to morphine. Additional support for this view was that an additional dose of morphine (8 mg/kg s.c.) in morphine-dependent rats was also ineffective in altering LCGU and in an antinociception (hot plate) test. Furthermore, plasma morphine levels in chronically treated animals were greater than those in acutely treated animals. Naloxone-precipitated morphine withdrawal enhanced LCGU, most notably in thalamic and limbic areas, but also in some hypothalamic and hindbrain regions. The findings identify brain areas that may be important in the opioid abstinence syndrome. Furthermore they suggest that adaptations in the brain produce tolerance to morphine, reflected in LCGU rates and latencies in the hot-plate test.