A novel, systemically active, selective galanin receptor type-3 ligand exhibits antidepressant-like activity in preclinical tests.
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.
Barr
Alasdair M
AM
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA, United States. albarr@interchange.ubc.ca <albarr@interchange.ubc.ca>
Kinney
Jefferson W
JW
Hill
Matthew N
MN
Lu
Xiaoying
X
Biros
Shannon
S
Rebek
Julius
J
Bartfai
Tamas
T
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*
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