Caratterizzazione del clofibrato agonista sintetico dei recettori dei proliferatori dei perossisomi (PPARα)in modelli animali di depressione ed ansia
type: CreativeWork
description: Depression is a severe mood disorder that affects a high percentage of the worldwide population. Unfortunately at least 40% of patients do not respond to the treatment. Therefore, considerable effort is invested in the development of alternative therapeutic approaches for the pharmacotherapy of depression. Peroxisome proliferator-activated receptors alpha (PPARα) are widely expressed in the brain and are activated by endogenous ligands like the fatty acid amides N-palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). Recent studies have been published on PPARα mediated behavioral effects, which suggests that PEA exerts anxiolytic and antidepressant-like effect in mice (Crupi et al., 2013, Yu et al., 2011). However no studies have been evaluated antidepressant-like effect of synthetic PPARα agonists. Thus, the aim of our study was to characterize the pharmacological profile of synthetic PPARα agonists as clofibrate by motor activity test to evaluate possible motor impairments, the forced swim test (FST) for the antidepressant activity, the elevated plus maze (EPM) and the social interaction test (SI) for anxiolytic like effects. The standard antidepressant drugs used in FST (fluoxetine 5mg/kg and amitriptyline 15 mg/kg, i.p) induced a significant increase of the duration of swimming respect to the vehicle-treated control group. Also the sub-chronic treatment with clofibrate (25 mg/kg, i.p) significantly increased swimming time and decreased immobility time in the FST with respect to vehicle-treated control group. We also investigated the possible contribution of PPARα and the endocannabinoid system on antidepressant-like effect induced by clofibrate, fluoxetine and amitriptyline. Acute administration of the specific PPARα antagonist MK886 (1 mg/kg, i.p) or the CB1 antagonist/inverse agonist SR141716A (1 mg/kg, i.p) did no antagonize the antidepressant-like effect induced by classical antidepressant drugs. In contrast the antidepressant-like affects of clofibrate …
abstract: Depression is a severe mood disorder that affects a high percentage of the worldwide population. Unfortunately at least 40% of patients do not respond to the treatment. Therefore, considerable effort is invested in the development of alternative therapeutic approaches for the pharmacotherapy of depression. Peroxisome proliferator-activated receptors alpha (PPARα) are widely expressed in the brain and are activated by endogenous ligands like the fatty acid amides N-palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). Recent studies have been published on PPARα mediated behavioral effects, which suggests that PEA exerts anxiolytic and antidepressant-like effect in mice (Crupi et al., 2013, Yu et al., 2011). However no studies have been evaluated antidepressant-like effect of synthetic PPARα agonists. Thus, the aim of our study was to characterize the pharmacological profile of synthetic PPARα agonists as clofibrate by motor activity test to evaluate possible motor impairments, the forced swim test (FST) for the antidepressant activity, the elevated plus maze (EPM) and the social interaction test (SI) for anxiolytic like effects. The standard antidepressant drugs used in FST (fluoxetine 5mg/kg and amitriptyline 15 mg/kg, i.p) induced a significant increase of the duration of swimming respect to the vehicle-treated control group. Also the sub-chronic treatment with clofibrate (25 mg/kg, i.p) significantly increased swimming time and decreased immobility time in the FST with respect to vehicle-treated control group. We also investigated the possible contribution of PPARα and the endocannabinoid system on antidepressant-like effect induced by clofibrate, fluoxetine and amitriptyline. Acute administration of the specific PPARα antagonist MK886 (1 mg/kg, i.p) or the CB1 antagonist/inverse agonist SR141716A (1 mg/kg, i.p) did no antagonize the antidepressant-like effect induced by classical antidepressant drugs. In contrast the antidepressant-like affects of clofibrate …
author: MAMELI, ALESSANDRA
language: ita
keywords: PEA, PPARα, ansia, anxiety, clofibrate, clofibrato, depression, depressione, Settore BIO/14 - Farmacologia
date published: 2015-05-07
date modified: 2026-07-24T01:30:09Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11584/266623