The effect of the serotonergic system on opioid withdrawal-like syndrome in a mouse model of cholestasis
There is a marked elevation of endogenous opioid levels in plasma of human subjects with biliary cirrhosis as well as animal model of cholestasis. In addition, development of morphine tolerance and dependence has been shown to be inhibited by drugs which reduce brain serotonin levels. However, intra...
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Published in | Human psychopharmacology Vol. 15; no. 6; pp. 423 - 428 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.08.2000
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Subjects | |
Online Access | Get full text |
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Summary: | There is a marked elevation of endogenous opioid levels in plasma of human subjects with biliary cirrhosis as well as animal model of cholestasis. In addition, development of morphine tolerance and dependence has been shown to be inhibited by drugs which reduce brain serotonin levels. However, intracerebroventricular injection of serotonin increases the morphine analgesia. In the present study we have investigated the role of the serotonergic pathway in determining the withdrawal syndrome in a mouse model of cholestasis. There were three experimental groups: unoperated mice, sham operated mice and mice in which the main bile duct was ligated. Physical dependency was assessed by precipitating a withdrawal syndrome (writing, climbing, rearing, grooming and jumping) by naloxone (2 mg/kg) 5 days after induction of cholestasis. In separate experimental same groups, the antinociception was evaluated by the tail flick latency (TFL) test. Administration of serotonin receptors antagonists, cyproheptadine (10 mg/kg), methysergide (6 mg/kg) and ondansetron (10 mg/kg) attenuated withdrawal signs and decreased the antinociception. However, treatment by fluoxetine (15 mg/kg), an inhibitor of serotonin reuptake, increased the withdrawal signs and antinociception. These experiments lead us to conclude that the naloxone‐precipitated withdrawal signs which occur in the mouse model of cholestasis are potentially dependent on the serotonergic pathway. Copyright © 2000 John Wiley & Sons, Ltd. |
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Bibliography: | ark:/67375/WNG-FSTQJDK7-5 istex:CB030732E182D68631B7AF8F6C5C2D2AD658B91E ArticleID:HUP214 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0885-6222 1099-1077 |
DOI: | 10.1002/1099-1077(200008)15:6<423::AID-HUP214>3.0.CO;2-V |