Cue-induced changes in basal local cerebral glucose utilization 13 days after morphine sensitization in the Fischer 344 rat: relevance for drug craving

Abstract

The present experiment tested the hypothesis that some persistent neural adaptation develops during the course of repeated sensitizing doses of morphine administered to rats. A sub-hypothesis was that this imprint would be of greater magnitude in the presence of morphine-conditioned cues. In order to test these hypotheses basal local cerebral metabolic rates for glucose (LCMR glu) were determined 13 days after the last of four 10-mg/kg doses of morphine administered in 36 h to Fischer 344 male rats. LCMR glu was determined using the 2-deoxy- d-[1- 14C]glucose method (2-DG). Half of the rats, the conditioned group, were placed in the 2-DG chamber after each injection and half, the nonconditioned group, were placed in a neutral environment. A control group received only saline in lieu of morphine. All metabolic rates were determined in a nondrugged state. The major finding was large increases in metabolic rate throughout the forebrain in the sensitized rats. This was especially so in the conditioned group, 46 out of 93 areas examined had significant increases while in the nonconditioned group it was 25 out of 93. Both the core and shell of the nucleus accumbens showed significant elevations in metabolic rates in the presence of morphine cues but only the shell in the absence of the cues. There were no significant decreases in basal metabolic activity in any of the brain regions evaluated in either experimental group. The present finding suggests that changes in the brains of these morphine-sensitized rats may model the altered brain states responsible for drug craving in human drug addicts.