Quantifiable dose-dependent withdrawal after morphine discontinuation in a rat model.
We evaluated the intensity of the withdrawal symptoms after the discontinuation of the morphine infusion in rats. Opiate addiction was induced by progressively increasing intraperitoneal morphine infusion rates. The control group (Group 1) 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 were gradually increased by a factor of 1.4, 2, 2.8, and 4 on the second, third, fourth, and fifth days, respectively. The last rate was used for 48 h and then infusions were disconnected. Weight reduction, food consumption, and water intake were used for evaluation of withdrawal. All morphine groups showed a significant reduction of body weight during the 4 postdiscontinuation days and a decline in food and water intake on the first postdiscontinuation day. All changes were dependent on the morphine infusion concentration. No changes were observed in the control group. We suggest that the rat model used in this study may be utilized for quantification of spontaneous withdrawal.
The Department of Anesthesiology, New York University Medical Center, 550 First Ave., New York, NY 10016, USA. levl@hotmail.com
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L
Langerman
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Piscoun
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Bansinath
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Shemesh
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Turndorf
G J
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Grant
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009021:Morphine Dependence / Q000523:psychology*; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D015431:Weight Loss / Q000187:drug effects
D009294:Narcotics; D009020:Morphine