title: Enduring attenuation of norepinephrine synaptic availability and augmentation of the pharmacological and behavioral effects of desipramine by repeated immobilization stress.
abstract: Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent increase in noradrenergic activity in the anterior aspects of the anterolateral bed nucleus of the stria terminalis (alBNST). This increase in noradrenergic activity results from both enhanced synthesis and reuptake of norepinephrine (NE). It leads to a decrease in the synaptic availability of NE, which elicits an augmented noradrenergic response to the inhibitors of NE reuptake (NRIs), such as desipramine (DMI), an antidepressant. The enduring depression-like behavior and the augmentation of the climbing behavior seen in repeatedly stressed rats following subchronic administration of DMI in the forced swimming test (FST) might be explained by a dysregulation of noradrenergic transmission observed in alBNST. Taken together, we propose that dysregulation of noradrenergic transmission such as the one described in the present work may represent a mechanism underlying major depressive disorders (MDD) with melancholic features in humans.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Gonzáles
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ana Pamela
authors.initials: AP
authors.lastname: Miranda
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Horacio
authors.initials: H
authors.lastname: Orrego
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Silva
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: mforray@uc.cl.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Forray
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000523:psychology*; D012686:Septal Nuclei / Q000187:drug effects* / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000697:Central Nervous System Stimulants; D000661:Amphetamine; D003891:Desipramine; D009638:Norepinephrine
keywords: Amphetamine (PubChem CID: 3007); Anxiety; Bed nucleus of the stria terminalis; Depression; Desipramine (PubChem CID: 2995); Forced swimming test; Microdialysis; Norepinephrine release; RX821002 (PubChem CID: 108094)