Modulation of preproenkephalin mRNA levels in brain regions and spinal cord of rats treated chronically with morphine.

The effect of morphine tolerance/dependence and abstinence on the preproenkephalin (PPE) gene expression was determined in brain regions and spinal cord of the rat. Male Sprague-Dawley rats were rendered tolerant and physically dependent on morphine by SC implantation of six pellets, each containing 75 mg of morphine base, during a 7-day period. Placebo pellet-implanted rats served as controls. In tolerant rats, the pellets were left in place at the time of sacrifice whereas in abstinent rats, the pellets were removed 16 h prior to sacrificing. The levels of PPE mRNA were determined in brain regions (striatum, cortex, pons-medulla, hypothalamus, amygdala, and midbrain) and spinal cord. The levels of PPE mRNA increased significantly in the cortex (62%) and the spinal cord (352%) of morphine-tolerant rats when compared to placebo pellet-implanted control rats. In other brain regions, the levels of PPE mRNA in placebo and morphine-tolerant rats did not differ. On the other hand, in morphine-abstinent rats, the levels of PPE mRNA increased in the striatum (62%) and hypothalamus (34%) but were decreased in pons-medulla (68%), midbrain (51%), and spinal cord (36%) in comparison to the placebo controls. The results clearly demonstrate differential changes in enkephalin gene expression in brain regions and spinal cord of the abstinent and nonabstinent morphine-tolerant/dependent rats.