title: Role of TrkB in the anxiolytic-like and antidepressant-like effects of vagal nerve stimulation: Comparison with desipramine.
abstract: A current hypothesis regarding the mechanism of antidepressant (AD) action suggests the involvement of brain-derived neurotrophic factor (BDNF). Consistent with this hypothesis, the receptor for BDNF (and neurotrophin 4/5 (NT-4/5)), Tropomyosin-related kinase B (TrkB), is activated in rodents by treatment with classical AD drugs. Vagal nerve stimulation (VNS), a therapy for treatment resistant depression (TRD), 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 using its inhibitor, K252a. Anxiolytic-like and AD-like effects were analyzed using the novelty suppressed feeding test (NSFT) and forced swim test (FST), respectively. K252a blocked the anxiolytic-like effect of chronic VNS treatment and the AD-like effect of acute VNS treatment. By contrast, blocking TrkB did not prevent either the anxiolytic-like or AD-like effect of chronic treatment with desipramine (DMI), a selective noradrenergic reuptake inhibitor; it did, however, block the acute effect of DMI in the FST. To examine whether the activation of TrkB caused by either VNS or DMI is ligand-dependent, use was made of TrkB-Fc, a molecular scavenger for ligands of TrkB. Intraventricular administration of TrkB-Fc blocked the acute activation of TrkB induced by either treatment, indicating that treatment-induced activation of this receptor is ligand-dependent. The behavioral results highlight differences in the involvement of TrkB in the chronic effects of an AD drug and a stimulation therapy as well as its role in acute versus chronic effects of DMI.
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, TX, USA. Electronic address: ashah69@jhmi.edu.
authors.forename: A P
authors.initials: AP
authors.lastname: Shah
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, TX, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Carreno
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, TX, USA.
authors.forename: Y A
authors.initials: YA
authors.lastname: Chung
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, TX, USA; South Texas Veterans Health Care System (STVHCS), Audie L. Murphy Division, San Antonio, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Frazer
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001008:Anxiety Disorders / Q000378:metabolism* / Q000628:therapy*; D002227:Carbazoles / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism* / Q000628:therapy*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055536:Vagus Nerve Stimulation / Q000379:methods
chemical_list: D018759:Adrenergic Uptake Inhibitors; D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D020813:Receptor, trkB; D003891:Desipramine
keywords: BDNF; TrkB; antidepressants; depression; desipramine; vagal nerve stimulation