Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling

• Published in: Psychopharmacologia 2010-08, Vol.211 (3), p.291-301
• Main Authors: Chiba, Shuichi, Numakawa, Tadahiro, Ninomiya, Midori, Yoon, Hyung Shin, Kunugi, Hiroshi
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Antidepressants; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Brain-Derived Neurotrophic Factor - metabolism; Depression; Depression - drug therapy; Disease Models, Animal; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Drug therapy; Ergolines - administration & dosage; Ergolines - pharmacology; Fluvoxamine - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Mitogen-Activated Protein Kinase 3 - metabolism; Mood disorders; Neuropharmacology; Neurosciences; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Inbred WKY; Rats, Wistar; Signal Transduction - drug effects; Up-Regulation - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-010-1894-8

Rationale Dopamine agonists have been implicated in the treatment of depression. Cabergoline is an ergot derivative with a high affinity to dopamine D 2 -like receptors; however, there have been few preclinical studies on its antidepressant-like effects. Materials and methods Behavioral effects of cabergoline were examined in rats using forced swimming (FST), novelty-suppressed feeding (NST), open field (OFT), and elevated-plus maze (EPT) tests. In a single treatment paradigm, behaviors of rats were analyzed 4 h after single injection of cabergoline (s.c., 0–4 µmol/kg). In a repeated-treatment paradigm, OFT, EPT, and FST were conducted on days 11, 12, and13–14, respectively, during daily cabergoline injections (s.c., 0.5 µmol/kg), and then hippocampus was removed 24 h after the last injection. NST was conducted in a separate experiment at day 14. Western blotting was used for the analysis of the protein levels of brain-derived neurotrophic factor (BDNF) and the activation of intracellular signaling molecules. Results Single injection of cabergoline demonstrated decreased immobility in FST and distance traveled during 0–10 min in OFT, while time spent and entry into open arms were increased at 4 µmol/kg. When cabergoline was repeatedly administered, immobility in FST and the latency of feeding in NSF were significantly reduced, while vertical movement was increased in OFT. The time in closed arms was tended to be decreased in EPT. Expression of BDNF and activation of extracellular signal-regulated kinase 1 were up-regulated after the chronic administration of cabergoline. Conclusions Cabergoline exerts antidepressant- and anxiolytic-like effects, which may be mediated by potentiation of intracellular signaling of BDNF.