title: Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.
abstract: Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Antunes
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Jossana Rodrigues
authors.initials: JR
authors.lastname: Ruff
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Dieniffer
authors.initials: D
authors.lastname: de Oliveira Espinosa
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Manuela Bastos
authors.initials: MB
authors.lastname: Piegas
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Maicon Lenon Otenio
authors.initials: ML
authors.lastname: de Brito
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Kellen Athaíde
authors.initials: KA
authors.lastname: Rocha
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: de Gomes
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: André Tiago Rossito
authors.initials: AT
authors.lastname: Goes
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Leandro Cattelan
authors.initials: LC
authors.lastname: Souza
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Donato
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
authors.forename: Silvana Peterini
authors.initials: SP
authors.lastname: Boeira
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil. Electronic address: cristianoricardojesse@yahoo.com.br.
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
mesh_terms: D000324:Adrenocorticotropic Hormone; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D013550:Swimming / Q000502:physiology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009478:Neuropeptide Y; D006897:Hydroxyindoleacetic Acid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: BDNF; Hypothalamic–pituitary–adrenocortical; Indoleamine 2,3-dioxygenase; Kynurenine; Neurotrophins; Serotonin