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center : Isfahan University of Medical Sciences
Document Type : Latin Dissertation
Language of Document : English
Record Number : 102792
Doc. No : T12393
Call number : ‭QV,77.5,S125e,2010‬
Main Entry : Sadeghi, Hossein
Title & Author : Evaluation of effects of intracerebroventricular and intrathecal administration of three- selected antidepressants on carrageenan- induced paw edema in rats and involving mechanisms in expression of theses effectc. Hossein Sadeghi/حسین صادقی
College : Schools, Pharmacy
Date : , 2010
Degree : Pharmacology, Ph.D
Page No : xix, 127 p.: ill ( som col ), diag., tab
Note : This thesis is also a resesarch project with project ID 386382
Note : Orginal Works
Abstract : Introduction: Antidepressants are widely used in the management of various types of pain including neuropathic and inflammatory pains in addition to treatment of psychiatric disorders. Anti-inflammatory effects of some antidepressants have been reported in a number of studies, but there is no information about the role of central sites in these effects of antidepressants. Thus, the aim of present study was to investigate the role of central mechanisms in the anti-inflammatory effect of three-selected anti-depressants with different mechanisms of action. Material and methods: At first, fluvoxamine, maprotiline, and amitriptyline were injected intraperitoneally 30 min before subplantar injection of carrageenan and the degree of paw swelling was evaluated 4 h after carrageenan. Next, different doses of the indicated antidepressants were administered intracerebroventricularly and intrathecally 30 min prior to carrageenan injection and the volume of paw was measured 4 h after carrageenan. In each part of the study, that the antidepressants injected was effective in reducing paw edema, the paw tissues were collected for: pathologic examination, determination of the activity of MPO and the levels of IL-l13 and TNF-a in the carrageenan injected paws. Finally, in order to assess the possible involvement of some receptors in the inhibitory effects of the indicated antidepressants on carrageenan-induced paw edema, animals were pretreated with propranolol (a non-selective (3-adrenoreceptor antagonist), yohimbine (an aradrenoreceptor antagonist) and prazosin (an a ra2-adrenoreceptor antagonist) 30 min prior to i.p. injection of maprotiline and amitriptyline. Naloxone (a non-selective opioid receptor antagonist) was co-administrated with maprotiline and amitriptyline. Mifeprisrone, a glucocorticoid receptors (GR) antagonist, was also injected 30 min before fluvoxamine and maprotiline.Results: Intraperitoneal injection of fluvoxamine (12.5, 25 and 50 mg/kg), maprotiline (12.5, 25 and 50 mg/kg) and amitriptiline (40 and 80 mg/kg) significantly reduced the paw inflammation according to the paw volumes, the activity of MPO and the levels of IL-1f3 and TNF-a in the paw tissues. Intracerebroventricular injection of maprotiline and amitriptyline also considerably reduced the volume of paw edema, the activity of MPO, and the levels of IL-I3. Intracerebroventricular injection of fluvoxamine did not show any effect on the volume of paw edema, compared to control group. None of the applied antidepressants was effective in reducing paw inflammation after intrathecal application. Moreover, among the applied antagonists only mifepristone, a glucocorticoid receptors antagonist, noticeably reversed the anti-inflammatory activity of fluvoxamine. Discussion: Our findings verified the previous studies about the anti-inflammatory effect of fluvoxamine, maprotiline and amitriptyline on the carrageenan-induced paw edema in rats and demonstrated that the supraspinal mechanisms have an important role in these effects of maprotiline and amitriptyline. Our results also ruled out the possible participation of ░plaid and some important adrenergic receptors in these effects of maprotiline and amitriptyline It seems possible that the anti-inflammatory effects of fluvoxamine are mainly mediated through the peripheral sites and glucocorticoid receptors are involved in these effects of fluvoxamine. We also demonstrated that the suppressing effects of the selected antidepressants on the PMN leucocytes infiltration and the production of pro-inflammatory cytokines such as IL-113 and TNF-a participate in their anti-inflammatory activities..
Descriptor : 1. Antidepressive Agents.- Descriptors: Antidepressive Agents
: Amitriptyline
: Fluvoxamine
: Maprotiline
: Injections, Intraperitoneal
: Infusions, Intraventricular
Added Entry : Hajhashemi, Valiollah, Supervisor
: Minaiyan, Mohsen, Supervisor
: Movahedian, Ahmad, Supervisor
: Talebi, Ardeshir, Supervisor
Translated Title Supplied by Cataloguer : ارزیابی اثرات تزریق داخل بطنی و داخل نخاعی سه داروی ضد افسردگی انتخاب شده بر التهاب ایجاد شده توسط کاراژینان در پای رات و مکانیسم درگیر در بروز این اثرات
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Evaluation of effects of intracerebroventricular and intr...
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