title: A role for galanin N-terminal fragment (1-15) in anxiety- and depression-related behaviors in rats.
abstract: BACKGROUND
  Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1-15)] in anxiety- and depression-related behavioral tests in rats.
  
  
  METHODS
  The effect of GAL(1-15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1-15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1-15) were also studied in the cell line RN33B.
  
  
  RESULTS
  GAL(1-15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1-15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1-15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1-15) decreased 5-HT immunoreactivity more strongly than GAL.
  
  
  CONCLUSIONS
  Our results indicate that GAL(1-15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety.
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
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, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
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, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
authors.forename: Manuel
authors.initials: M
authors.lastname: Narváez
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
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, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
authors.forename: Concepción
authors.initials: C
authors.lastname: Parrado
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
authors.forename: José Angel
authors.initials: JA
authors.lastname: Narváez
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín).
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, España (PhD Millón, Flores-Burgess, M Narváez, Parrado, JA Narváez, and Díaz-Cabiale); Department of Neuroscience, Karolinska Institute, Stockholm, Sweden (PhD Borroto-Escuela and Fuxe); Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos s/n, 29071 Málaga, España (PhD Santín). zaida@uma.es.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Díaz-Cabiale
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D002461:Cell Line, Transformed; D003623:Dark Adaptation / Q000187:drug effects; D003863:Depression / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D019004:Galanin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D044091:Receptor, Galanin, Type 1 / Q000172:deficiency / Q000235:genetics; D044092:Receptor, Galanin, Type 2 / Q000172:deficiency / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D012701:Serotonin; D019004:Galanin
keywords: anxiety; depression; galanin