Orexin A injection into the ventral medial prefrontal cortex induces antidepressant-like effects: Possible involvement of local Orexin-1 and Trk receptors.

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.