title: Galanin (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT: involvement of the raphe-hippocampal 5-HT neuron system.
abstract: Galanin N-terminal fragment (1-15) [GAL(1-15)] is associated with depression-related and anxiogenic-like effects in rats. In this study, we analyzed the ability of GAL(1-15) to modulate 5-HT1A receptors (5-HT1AR), a key receptor in depression. GAL(1-15) enhanced the antidepressant effects induced by the 5-HT1AR agonist 8-OH-DPAT in the forced swimming test. These effects were stronger than the ones induced by Galanin (GAL). This action involved interactions at receptor level since GAL(1-15) affected the binding characteristics and the mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe. The involvement of the GALR2 was demonstrated with the GALR2 antagonist M871. Proximity ligation assay experiments indicated that 5-HT1AR are in close proximity with GALR1 and GALR2 in both regions and in raphe RN33B cells. The current results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT acting on 5-HT1AR operating as postjunctional or as autoreceptors. These results may give the basis for the development of drugs targeting potential GALR1-GALR2-5-HT1AR heteroreceptor complexes linked to the raphe-hippocampal 5-HT neurons for the treatment of depression.
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Departamento de Fisiología, 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, Departamento de Fisiología, 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, Departamento de Fisiología, 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: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Departamento de Psicobiología, 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, Departamento de Fisiología, Campus de Teatinos s/n, 29071, Málaga, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Gago
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Departamento de Fisiología, 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 Medicina, Departamento de Fisiología, Campus de Teatinos s/n, 29071, Málaga, Spain. zaida@uma.es.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Díaz-Cabiale
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000378:metabolism; D019004:Galanin / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; C000603588:M871 peptide; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D017366:Serotonin Receptor Agonists; C086813:galanin (1-15); D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin
keywords: 5-HT1A receptors; Depression; Galanin; Galanin (1–15); Heteroreceptor complexes