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Effects of fluoxetine and LY 365265 on tolerance to the analgesic effect of morphine in rats

Effects of fluoxetine and LY 365265 on tolerance to the analgesic effect of morphine in rats

JournalActa Physiologica Hungarica
PublisherAkadémiai Kiadó
ISSN0231-424X (Print)
1588-2683 (Online)
SubjectPhysiology
IssueVolume 98, Number 2/June 2011
CategoryOriginal Papers
Pages205-213
DOI10.1556/APhysiol.98.2011.2.12
Subject GroupMedicine
Online DateThursday, May 26, 2011
Authors
Ercan Ozdemir1, 4 Email for ercan_ozdemir@hotmail.com, I. Bagcivan2, S. Gursoy3, A. Altun2, N. Durmus2

1Cumhuriyet University School of Medicine Departments of Physiology Sivas Turkey
2Cumhuriyet University School of Medicine Departments of Pharmacology Sivas Turkey
3Cumhuriyet University School of Medicine Departments of Anesthesiology and Reanimation Sivas Turkey
4Cumhuriyet University School of Medicine Department of Physiology 58140 Sivas Turkey

Abstract

Morphine is widely used to treat chronic pain, however its utility is hindered by the development of tolerance to its analgesic effects. The aim of this study was to investigate effects of fluoxetine, a specific serotonin (5-HT) reuptake inhibitor, and LY 367265, an inhibitor of the 5-HT transporter and 5-HT2A receptor antagonist, on tolerance induced to the analgesic effect of morphine in rats. The study was carried out on male Wistar Albino rats (weighing 170–190 g). To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After last dose of morphine, injected on day 4, morphine tolerance was evaluated. The analgesic effects of fluoxetine (10 mg/ kg; i.p.), LY 367265 (3 mg/kg; i.p.) and morphine were considered at 30-min intervals by tail-flick and hot-plate tests. The results showed that fluoxetine and LY 367265 significantly attenuated the development and expression of morphine tolerance. The maximal antinociceptive effects were obtained 30 min after administration of fluoxetine and 60 min after administration of LY 367265. In conclusion, we observed that co-injection of morphine with fluoxetine and LY 367265 increased the analgesic effects of morphine and delayed development of tolerance to morphine analgesia.

Keywords
antinociception, morphine, tolerance, fluoxetine, LY 367265, hot-plate test, tail-flick test
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