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2.
Mol Neurobiol ; 55(10): 7949-7960, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29488138

RESUMO

Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.


Assuntos
Calcineurina/metabolismo , Cotinina/farmacologia , Depressão/tratamento farmacológico , Depressão/psicologia , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hipocampo/metabolismo , Óleos/farmacologia , Administração Intranasal , Animais , Comportamento Animal , Condicionamento Psicológico , Cotinina/administração & dosagem , Cotinina/uso terapêutico , Euphausiacea/química , Camundongos Endogâmicos C57BL , Modelos Biológicos , Óleos/administração & dosagem , Sertralina/farmacologia
3.
Front Neurosci ; 12: 952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30618579

RESUMO

Restraint stress (RS) is a condition affecting millions of people worldwide. The investigation of new therapies to alleviate the consequences of prolonged RS is much needed. Cotinine, a nicotine-derivative, has shown to prevent the decrease in cerebral synaptic density, working memory deficits, anxiety, and depressive-like behavior after prolonged restraint stress (RS) in mice. Furthermore, post-treatment with cotinine reduced the adverse effects of chronic RS on astrocyte survival and architecture. On the other hand, the nutritional supplement krill oil (KO), has shown to be beneficial in decreasing depressive-like behavior and oxidative stress. In this study, in the search for effective preventative treatments to be used in people subjected to reduced mobility, the effect of co-treatment with cotinine plus KO in mice subjected to prolonged RS was investigated. The results show that cotinine plus KO prevented the loss of astrocytes, the appearance of depressive-like behavior and cognitive impairment induced by RS. The use of the combination of cotinine plus KO was more effective than cotinine alone in preventing the depressive-like behavior in the restrained mice. The potential use of this combination to alleviate the psychological effects of reduced mobility is discussed.

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