RESUMO
Major depressive disorder is the most severe and debilitating disease among psychiatric illnesses. The abrupt interruption of antidepressant treatment may lead to a complex physiological and neuropsychiatric syndrome. The organoselenium compound (MeOPhSe)2 has been reported to have neuroprotective properties in animal models. The study aimed to investigate the effects of single or repeated administration of (MeOPhSe)2 on depressive-like behavior and if the compound administration, and its discontinuation, may affect the anxiolytic-like phenotype in Swiss mice. The results showed that repeated intragastric administration of (MeOPhSe)2 (dose range: 0.1-5mg/kg), different from a single administration, reduced the immobility time in the mouse tail suspension test. A single administration of (MeOPhSe)2 at a dose of 5mg/kg decreased the immobility time, increased the swimming time and did not alter the climbing behavior in the modified forced swimming test (mFST). Repeated administration of (MeOPhSe)2 decreased the immobility time, did not alter the swimming time and increased the climbing behavior in the mouse mFST. Repeated administration of (MeOPhSe)2 at a dose of 5mg/kg elicited a mouse anxiolytic-like phenotype in the elevated plus maze and light-dark tests. Markers of hepatic and renal function tests were not altered by repeated administration of (MeOPhSe)2 to mice. The findings indicate that a single or repeated administration of (MeOPhSe)2 elicited an antidepressant-like action in mice. Moreover, repeated treatment with (MeOPhSe)2 produced an anxiolytic-like action in mice and its profile remained stable after discontinuation.
Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Resposta de Imobilidade Tônica/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Testes de Função Renal , Testes de Função Hepática , Masculino , CamundongosRESUMO
Depression and pain comorbidity represent a neuropsychiatric condition with substantial socioeconomic impact to society. The commonly used antidepressants and analgesics to treat this comorbidity have shown restricted clinical efficacy. In this way, the aim of this study was to investigate the behavioral, biochemical and neurochemical effects of a p,p'-methoxyl-diphenyl diselenide (OMePhSe)2 supplemented diet on pain-depression dyad induced by reserpine in rats. Adult Wistar rats were fed with 10mg (MeOPhSe)2 per kg of rat chow supplemented diet for 30 days. Pain-depression dyad was induced by daily subcutaneous reserpine injection (0.5mg/kg for three consecutive days) from 22 to 24 day of (MeOPhSe)2 supplementation. The results showed that the reserpine injected rats had behavior phenotypes typical of depression-pain dyad and the (MeOPhSe)2-supplemented diet protected against these modifications. Furthermore, the (MeOPhSe)2 dietary supplementation was effective against the increase in the prefrontal cortical MDA levels caused by reserpine. (MeOPhSe)2-supplemented diet triggered a per se augmentation of Nrf-2 levels. The [3H] serotonin uptake, [3H] glutamate uptake and release and MAO activity were not altered in the prefrontal cortices of rats from any experimental group. Therefore, the results indicate that protective effects of a (MeOPhSe)2-supplemented diet can be mediated, at least in part, by its antioxidant property.
Assuntos
Derivados de Benzeno/farmacologia , Depressão/complicações , Depressão/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Dor/complicações , Dor/tratamento farmacológico , Reserpina/farmacologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Derivados de Benzeno/uso terapêutico , Depressão/metabolismo , Depressão/fisiopatologia , Suplementos Nutricionais , Locomoção/efeitos dos fármacos , Masculino , Neuroquímica , Compostos Organosselênicos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Dor/metabolismo , Dor/fisiopatologia , Ratos , Ratos WistarRESUMO
The present study evaluated the antinociceptive and anti-inflammatory effects of per oral (p.o.) administration of salicylic acid-derivative organoselenium compounds in chemical models of nociception in mice. The compounds (50 mg/kg; p.o.) were administered 30 and 60 min before the nociceptive behavior and compared to the positive-control, acetylsalicylic acid (ASA; 200 mg/kg; p.o.). In addition, a dose-response curve (25-100 mg/kg) for compounds was carried out in the formalin test. When assessed in the chemical models, acetic acid-induced writhing behavior, formalin and glutamate tests, the compounds showed the following antinociceptive profile 1B>2B>1A>2A, suggesting a chemical structure-dependent relationship. Then, the anti-inflammatory properties and toxicological potential of compound 1B were investigated. Compound 1B, similar to the positive-control, ASA, diminished the edema formation and decreased the myeloperoxidase activity induced by croton oil (2.5%) in the ear tissue. The results also indicate that a single oral administration of 1B caused neither signs of acute toxicity nor those of gastrointestinal injury. The administration of 1B did not alter the water and food intakes, plasma alanine and aspartate aminotransferase activities or urea levels and cerebral or hepatic δ-aminolevulinate dehydratase activity. Salicylic acid-derivative organoseleniums, mainly compound 1B, have been found to be novel compounds with antinociceptive/anti-inflammatory properties; nevertheless, more studies are required to examine their therapeutic potential for pain treatment.