TIME-COURSE OF MORPHINE-WITHDRAWAL AND PREPROENKEPHALIN GENE-EXPRESSION IN THE PERIAQUEDUCTAL GRAY OF RATS

We have previously reported the increase of preproenkephalin (PPE) mRN A in the caudal periaqueductal gray (PAG) of rats during morphine with drawal. In this study, it was further evidenced that PPE mRNA in the c audal FAG was not increased by various kinds of stressor, suggesting t hat the increase in PPE mRNA in the caudal FAG is specific to morphine withdrawal. In order to investigate the physiological significance of the increase of PPE mRNA in the caudal FAG, we compared the time cour se of the increase of PPE mRNA in the caudal FAG with that of naloxone -precipitated or spontaneous morphine withdrawal signs. The increase o f plasma corticosterone (PCS: 52 and 52 mu g/100 ml; control group, 18 and 15 mu g/100 ml) and body weight loss (-6 and -9%; control group, 0 and -1%) were observed but PPE mRNA increase was not detected 1 and 2 h after naloxone in morphine treated rats. PPE mRNA increased by 37 to 56%, while PCS elevation and body weight loss gradually diminished 4 h to 2 days after naloxone. A total of 12 h after spontaneous withdr awal, PCS was prominently increased (51 mu g/100 ml; control group, 12 mu g/100 ml), but body weight and PPE mRNA were not affected. One day after spontaneous withdrawal, PCS elevation (38 mu g/100 ml; control group, 8 mu g/100 ml) and body weight loss (-5%; control group, +3%) w ere observed and PPE mRNA also increased by 42%. Two to 3 days after t he final morphine injection, PCS recovered to control level and body w eight loss gradually disappeared, while PPE mRNA was still increased b y 74 to 46%. These results suggest that PPE gene expression in the cau dal FAG is stimulated in the recuperative phase of these morphine with drawal signs. (C) 1998 Elsevier Science B.V.