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

Brain Structure & Function
Carmelo MillónZaida Díaz-Cabiale

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.

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Citations

Feb 22, 2018·Reviews in the Neurosciences·Diego GuidolinLuigi F Agnati
May 14, 2019·Journal of Psychopharmacology·Carmelo MillónZaida Díaz-Cabiale
Dec 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Swapnali BardeTomas G M Hökfelt
Mar 6, 2019·Frontiers in Endocrinology·Diego GuidolinLuigi F Agnati
Jan 15, 2019·Journal of Neural Transmission·Dasiel O Borroto-Escuela, Kjell Fuxe
Jun 20, 2019·International Journal of Molecular Sciences·Elise WoutersChristophe P Stove
May 6, 2020·Biologics : Targets & Therapy·Desalegn Getnet DemsieAbere Tilahun Bantie
Mar 9, 2017·Frontiers in Cellular Neuroscience·Dasiel O Borroto-EscuelaKjell Fuxe
Jun 6, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dasiel O Borroto-EscuelaKjell Fuxe
Mar 23, 2021·Pharmacology & Therapeutics·Katarzyna MlyniecGabriel Nowak
May 30, 2019·ACS Chemical Neuroscience·Catherine A MarcinkiewczThomas L Kash
Dec 11, 2021·The International Journal of Neuropsychopharmacology·Antonio Flores-BurgessZaida Díaz-Cabiale

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