Quantifiable dose-dependent withdrawal after morphine discontinuation in arat model

We evaluated the intensity of the withdrawal symptoms after the discontinua tion of the morphine infusion in rats. Opiate addiction was induced by prog ressively increasing intraperitoneal morphine infusion rates. The control g roup(Group l)received normal saline. The initial morphine rates were 1, 4, and 16 mg kg (-1) h for Groups 2, 3, and 4, respectively. Infusion rates we re gradually increased by a factor of 1.4, 2, 2.8, and 4 on the second, thi rd, fourth, and fifth days. respectively. The last rate was used for 48 h a nd then infusions were disconnected. Weight reduction, food consumption, an d water intake were used for evaluation of withdrawal. All morphine groups showed a significant reduction of body weight during the 4 postdiscontinuat ion days and a decline in food and water intake on the first postdiscontinu ation day. All changes were dependent on the morphine infusion concentratio n. No changes were observed in the control group. We suggest that the rat m odel used in this study may be utilized for quantification of spontaneous w ithdrawal. (C) 2001 Elsevier Science Inc. All rights reserved.