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1.
J Neural Transm (Vienna) ; 121(6): 671-82, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24463888

RESUMO

Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Piroxicam/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antidepressivos/farmacologia , Celecoxib , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Privação de Alimentos , Glutationa/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Norepinefrina/metabolismo , Piroxicam/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos , Sacarose/administração & dosagem , Sulfonamidas/farmacologia , Superóxido Dismutase/metabolismo , Natação/psicologia , Fatores de Tempo , Privação de Água
2.
Eur J Pharmacol ; 543(1-3): 181-9, 2006 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-16814279

RESUMO

This study evaluates the antipyretic activity of nimesulide, a cyclooxygenase (COX-2) selective inhibitor in rats. The effects of nimesulide on lipopolysaccharide (LPS)-induced cerebrospinal prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) and on plasma tumor necrosis factor-alpha (TNF-alpha) levels were also evaluated. Male Wistar rats received an i.p. injection of LPS, or i.c.v. injections of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), TNF-alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), arachidonic acid, PGE(2), PGF(2alpha), corticotrophin-releasing factor (CRF) or endothelin-1 (ET-1). Nimesulide or indomethacin administered i.p 30 min prior LPS, IL-1beta, IL-6, TNF-alpha or arachidonic acid reduced the febrile response and PGE(2) or PGF(2alpha) levels in LPS-febrile rats but did not modify PGE(2)-induced fever. Nimesulide, but not indomethacin, reduced the fever induced by MIP-1alpha, PGF(2alpha), CRF or ET-1. Plasma TNF-alpha levels in LPS-treated rats were also reduced by nimesulide. These findings confirm that the antipyretic effect of nimesulide differs from the antipyretic scenario with the non-selective cyclooxygenase blocker indomethacin. Additional mechanisms, including inhibition of increased plasma TNF-alpha, may contribute to its antipyretic activity in rats.


Assuntos
Analgésicos não Narcóticos/farmacologia , Temperatura Corporal/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Febre/prevenção & controle , Sulfonamidas/farmacologia , Animais , Ácido Araquidônico/metabolismo , Quimiocina CCL3 , Quimiocina CCL4 , Hormônio Liberador da Corticotropina/metabolismo , Dinoprosta/líquido cefalorraquidiano , Dinoprosta/metabolismo , Dinoprostona/líquido cefalorraquidiano , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Endotelina-1/metabolismo , Febre/sangue , Febre/líquido cefalorraquidiano , Febre/induzido quimicamente , Indometacina/farmacologia , Injeções Intraperitoneais , Injeções Intraventriculares , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Proteínas Inflamatórias de Macrófagos/metabolismo , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
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