Antidepressant-like effect of agmatine is not mediated by serotonin.
The aim of this study was to characterize the behavioral effects of systemically administered agmatine in animal models predictive of antidepressant- and anxiolytic-like activity and clarify whether the effects of agmatine depend on the intact serotonergic system. Only the highest dose of agmatine tested (50 mg/kg) decreased immobility of mice in the forced swimming test. The magnitude of the effect was slightly smaller than that of the tricyclic antidepressant imipramine (15 mg/kg). Agmatine did not change the locomotion of mice in the open field. Pretreatment with the tryptophane hydroxylase inhibitor PCPA for 3 days resulted in more than 70% drop in the tissue levels of 5-HT and 5-HIIA but did not counteract the antidepressant-like effect of agmatine. The administration of agmatine did not modify behavior of animals in the light-dark compartment test of anxiety. We conclude that the antidepressant-like effect of agmatine seems not to be mediated by the serotonergic system. We failed to confirm the reported anxiolytic-like activity of agmatine.
Krass
Maarja
M
Department of Physiology, University of Tartu, Tartu, Estonia.
Wegener
Gregers
G
Vasar
Eero
E
Volke
Vallo
V
D000376:Agmatine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; C020261:4-chlorophenylalanine methyl ester; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000376:Agmatine; D007099:Imipramine; D010134:Fenclonine