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Behav Brain Res ; 395: 112866, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32827568

RESUMEN

RATIONALE: Reduced levels of orexin-A (OXA) in the central nervous system (CNS) have been associated with the pathophysiology of depression and its exogenous administration promotes antidepressant-like effect. The mechanisms associated with these effects are, however, not yet known. Herein, we investigated the hypothesis that OXA effects could be associated with orexin 1 receptor (OX1R) and tyrosine receptor kinase B (TrkB) activation, in the ventromedial prefrontal cortex (vmPFC), a brain region that is central to depression neurobiology. OBJECTIVES: 1. To Investigate the effects induced by OXA administration into the vmPFC; 2. Evaluate the participation of OX1R and TrkB in behavioral responses induced by OXA. METHODS: Male Wistar rats received intra-vmPFC injections of OXA (10, 50 and 100 pmol/0.2 µL) and were exposed to the forced swimming test (FST) or the open field test (OFT). Independent groups received an intra-vmPFC injection of SB334867 (OX1R antagonist, 10 nmol/0.2 µL) or K252a (non-selective Trk antagonist, 10 pmol/0.2 µL), before local injection of OXA, and were exposed to the same tests. RESULTS: OXA injection (100 pmol/0.2 µL) into the vmPFC induced antidepressant-like effect, which was prevented by SB334867 and K252a pretreatments. CONCLUSION: OXA signaling in the vmPFC induces antidepressant-like effect in the FST which is dependent on OX1R and Trk receptors.


Asunto(s)
Depresión/tratamiento farmacológico , Orexinas/farmacología , Corteza Prefrontal/metabolismo , Animales , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Receptores de Orexina/efectos de los fármacos , Receptores de Orexina/metabolismo , Orexinas/administración & dosificación , Orexinas/metabolismo , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Wistar , Receptor trkB/metabolismo , Transducción de Señal/efectos de los fármacos , Estrés Psicológico
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