Agmatine produces antidepressant-like effects in two models of depression in mice

Neuroreport. 2002 Mar 25;13(4):387-91. doi: 10.1097/00001756-200203250-00005.


Agmatine produces an antidepressant-like effect when assessed in the forced swimming test (FST) and in the tail suspension test (TST) in mice (dose range 0.01-50 mg/kg, i.p.), without accompanying changes in ambulation in an open-field. I.c.v. injection of agmatine (1-100 nmol/site) also reduced the immobility time in the FST. Agmatine significantly enhanced the anti-immobility effect of imipramine, but did not affect that of MK-801. The anti-immobility effect of agmatine assessed in the FST was not affected by pre-treatment with prazosin. In contrast, agmatine's antidepressant-like effect was completely prevented by pre-treatment of animals with yohimbine, GMP or L-arginine. Taken together these data demonstrate that agmatine elicited a significant antidepressant-like effect through a mechanism that seems to involve an interaction with NMDA receptors, the L-arginine-nitric oxide pathway and alpha2-adrenoceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agmatine / pharmacology
  • Agmatine / therapeutic use*
  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Depression / drug therapy*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Female
  • Imipramine / therapeutic use
  • Male
  • Mice
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Receptors, N-Methyl-D-Aspartate
  • Agmatine
  • Nitric Oxide Synthase
  • Imipramine