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

• Published in: Brain Structure and Function Vol. 221; no. 9; pp. 4491 - 4504
• Main Authors: Millón, Carmelo, Flores-Burgess, Antonio, Narváez, Manuel, Borroto-Escuela, Dasiel O., Santín, Luis, Gago, Belen, Narváez, José Angel, Fuxe, Kjell, Díaz-Cabiale, Zaida
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2016; Springer Nature B.V
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - administration & dosage; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Dorsal Raphe Nucleus - drug effects; Dorsal Raphe Nucleus - metabolism; Galanin - administration & dosage; Galanin - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medicin och hälsovetenskap; Mental depression; Neurology; Neurons; Neurosciences; Original Article; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Peptides - administration & dosage; Rats; Rats, Sprague-Dawley; Receptor, Galanin, Type 1 - metabolism; Receptor, Galanin, Type 2 - antagonists & inhibitors; Receptor, Galanin, Type 2 - metabolism; RNA, Messenger - metabolism; Serotonergic Neurons - drug effects; Serotonergic Neurons - metabolism; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - pharmacology; Studies; Depression; Galanin (1–15); Heteroreceptor complexes; Galanin; 5-HT1A receptors
• ISSN: 1863-2653; 1863-2661; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-015-1180-y

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.