Role of TrkB in the Anxiolytic-like and Antidepressant-like Effectsof Vagal Nerve Stimulation: Comparison with Desipramine

摘要

A current hypothesis regarding the mechanism of antidepressant action suggests the involvement of brain derived neurotrophic factor (BDNF). Consistent with this hypothesis, the receptor for BDNF (and neurotrophin 4/5), Tropomyosin related kinase B (TrkB), is activated in rodents by treatment with classical antidepressant drugs. Vagal nerve stimulation (VNS), a therapy for treatment resistant depression, also activates TrkB in rodents. However, the role of this receptor in the therapeutic effects of VNS is unclear. In the current study, the involvement of TrkB in the effects of VNS was investigated in rats by using its inhibitor, K252a. Anxiolytic-like and antidepressant-like effects were analyzed using the novelty suppressed feeding test and forced swim test, respectively. K252a blocked the anxiolytic-like effect of chronic VNS treatment and the antidepressant-like effect of acute VNS treatment. By contrast, blocking TrkB did not prevent either the anxiolytic-like or antidepressant-like effect of chronic treatment with desipramine, a selective noradrenergic reuptake inhibitor; it did, however, block the acute effect of desipramine in the forced swim test. To examine whether the activation of TrkB caused by either VNS or desipramine is ligand-dependent, use was made of TrkB-Fc, a molecular scavengerfor ligands of TrkB. Intraventricular administration of TrkB-Fc blocked theacute activation of TrkB induced by either treatment, indicating thattreatment-induced activation of this receptor is ligand-dependent. Thebehavioral results highlight differences in the involvement of TrkB in thechronic effects of an antidepressant drug and a stimulation therapy as well asits role in acute versus chronic effects of desipramine.