title: A novel, systemically active, selective galanin receptor type-3 ligand exhibits antidepressant-like activity in preclinical tests.
abstract: The neuropeptide galanin is widely expressed in limbic nuclei in the brain, and plays an important role in the regulation of homeostatic and affective behaviors, in part through its modulation of central monoamine pathways. Recent evidence suggests that galanin and its receptors may be involved in the efficacy of various modalities of antidepressant treatments. We have previously demonstrated that systemically active, non-peptide galanin receptor type-1/2 agonists exhibit antidepressant-like effects in the rat forced swim test. Here we evaluate a novel galanin receptor type-3 (GalR3) antagonist in preclinical tests of anxiety and depression. At multiple doses, the compound displayed no effects in the elevated plus maze in mice. By contrast, the compound decreased time spent immobile in the tail suspension test by mice. Additionally, the GalR3 drug decreased time spent immobile in the forced swim test in rats, similarly to the effects of desipramine, yet did not increase locomotor activity in an open field test. These combined data from two species indicate that GalR3 receptor antagonists may exhibit antidepressant-like effects.
authors.affiliation: Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA, United States. albarr@interchange.ubc.ca <albarr@interchange.ubc.ca>
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.forename: Jefferson W
authors.initials: JW
authors.lastname: Kinney
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lu
authors.forename: Shannon
authors.initials: S
authors.lastname: Biros
authors.forename: Julius
authors.initials: J
authors.lastname: Rebek
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007097:Imines / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044093:Receptor, Galanin, Type 3 / Q000037:antagonists & inhibitors*
chemical_list: C514225:3-(3,4-dichlorophenylimino)-1-(6-methoxypyridin-3-yl)indolin-2-one; D000928:Antidepressive Agents; D007097:Imines; D007211:Indoles; D008024:Ligands; D011725:Pyridines; D044093:Receptor, Galanin, Type 3