title: Galanin (1-15) enhancement of the behavioral effects of Fluoxetine in the forced swimming test gives a new therapeutic strategy against depression.
abstract: The pharmacological treatment of major depression is mainly based on drugs elevating serotonergic (5-HT) activity. Specifically, selective 5-HT reuptake inhibitors, including Fluoxetine (FLX), are the most commonly used for treatment of major depression. However, the understanding of the mechanism of action of FLX beyond its effect of elevating 5-HT is limited. The interaction between serotoninergic system and neuropeptides signaling could be a key aspect. We examined the ability of the neuropeptide Galanin(1-15) [GAL(1-15)] to modulate the behavioral effects of FLX in the forced swimming test (FST) and studied feasible molecular mechanisms. The data show that GAL(1-15) enhances the antidepressant-like effects induced by FLX in the FST, and we demonstrate the involvement of GALR1/GALR2 heteroreceptor complex in the GAL(1-15)-mediated effect using in vivo rat models for siRNA GALR1 or GALR2 knockdown. Importantly, 5-HT1A receptors (5HT1A-R) also participate in the GAL(1-15)/FLX interactions since the 5HT1AR antagonist WAY100635 blocked the behavioral effects in the FST induced by the coadministration of GAL(1-15) and FLX. The mechanism underlying GAL(1-15)/FLX interactions affected the binding characteristics as well as the mRNA levels of 5-HT1A-R specifically in the dorsal hippocampus while leaving unaffected mRNA levels and affinity and binding sites of this receptor in the dorsal raphe. The results open up the possibility to use GAL(1-15) as for a combination therapy with FLX as a novel strategy for treatment of depression.
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Flores-Burgess
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Millón
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gago
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Narváez
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Department of Neurochemistry and Neuropharmacology, IIBB-CSIC,IDIBAPS,CIBERNED, Barcelona 08036, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Mengod
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Narváez
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Santín
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain. Electronic address: zaida@uma.es.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Díaz-Cabiale
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001345:Autoradiography; D003510:Cyclohexanes / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000627:therapeutic use*; D019004:Galanin / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000235:genetics / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D013550:Swimming / Q000523:psychology*
chemical_list: D000928:Antidepressive Agents; D003510:Cyclohexanes; D010446:Peptide Fragments; D010879:Piperazines; D034741:RNA, Small Interfering; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; C112802:WAY 101363; D005473:Fluoxetine; C086813:galanin (1-15); D019004:Galanin
keywords: 5-HT1A receptor; Depression; Fluoxetine; Galanin(1-15)