Time action profiles of regional cerebral glucose utilization during naloxone-precipitated morphine withdrawal

Time-dependent profiles of regional cerebral glucose utilization (RCGU) during morphine withdrawal (MW) were studied by varying the time of 2-deoxy-[14C]glucose (2-DG) administration after a maximal withdrawal-precipitating dose of naloxone was given to morphine-dependent rats. Heterogeneous and multiphasic time-action patterns of RCGU responses were found among 21 brain regions known to exhibit specific elevations in 2-DG labeling during MW. All MW-associated RCGU responses decreased when the interval between naloxone and 2-DG injection approximated the half-life of naloxone in the brain. Of the regions studied, time courses for metabolic responses in the lateral septum and lateral habenula most closely approximated the time course of naloxone availability in the brain. These results suggest that the earliest direct effects of naloxone on central nervous system metabolism in morphine-dependent rats occur in the lateral septum and lateral habenula.