A Role for Galanin N-Terminal Fragment (1-15) in Anxiety- and Depression-Related Behaviors in Rats

作者：Millon Carmelo; Flores Burgess Antonio; Narvaez Manuel; Borroto Escuela Dasiel O; Santin Luis; Parrado Concepcion; Narvaez Jose Angel; Fuxe Kjell; Diaz Cabiale Zaida^*

来源：International Journal of Neuropsychopharmacology, 2015, 18(3).

DOI：10.1093/ijnp/pyu064

• anxiety
• depression
• galanin

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 GAL 1 and GAL 2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1-15) effects with the GAL 2 receptor antagonist M871 and with an in vivo model of siRNA GAL 2 receptor knockdown or siRNA GAL 1 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 GAL 2 receptor was demonstrated with M871 and with the siRNA GAL 2 receptor knockdown rats. The PLA indicated the possible existence of GAL 1 and GAL 2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL 1 receptor knockdown rats the behavioral actions of GAL(1-15) disappeared, and in the siRNA GAL 2 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 GAL 1 and GAL 2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety.

• 出版日期2015-2