Metabolic Brain Disease

, Volume 33, Issue 5, pp 1721–1731 | Cite as

Antidepressant-like action of agmatine in the acute and sub-acute mouse models of depression: a receptor mechanism study

  • Zhao-Di Chen
  • Wen-Qiang Chen
  • Zhi-Yuan Wang
  • Dan-Ni Cao
  • Ning WuEmail author
  • Jin LiEmail author
Original Article


Previous studies have shown that agmatine, a potential neuromodulator or co-transmitter, exhibited antidepressant-like action in animal models, yet its mechanism, especially the receptor mechanism, remains unclear. In the present study, using efaroxan, a preferential antagonist of I1 imidazoline receptor (I1R) and yohimbine, an antagonist of α2 adrenergic receptor (α2AR), we investigated the roles of I1R and α2AR in agmatine’s antidepressant-like effect in acute and sub-acute depression models in mice. We found that in the tail-suspension test (TST) and the forced swimming test (FST), acute administration of agmatine (20 and 40 mg/kg, p.o.) significantly shortened the immobility time. Concurrent administration of efaroxan (1 mg/kg, i.p.) completely abolished the antidepressant-like effects of agmatine (40 mg/kg, p.o.) whereas yohimbine (5 mg/kg, i.p.) failed to exert similar effects, suggesting that the acute antidepressant-like effects of agmatine was mainly mediated by I1R but not α2AR. Additionally, in the learned helplessness (LH) test, repeated administration of agmatine (20 mg/kg, p.o., q.d.) for 5 days significantly decreased the escape latency and the number of escape failure, and these effects were respectively abolished by concurrent administration of efaroxan (0.5 mg/kg,i.p., q.d.) and yohimbine (3 mg/kg, i.p., q.d.) for 5 days, suggesting that the antidepressant-like action of agmatine in the LH test was achieved via the activation of both I1R and α2AR. In summary, we found that the antidepressant-like effects of agmatine in the TST and the FST were mediated by activating I1R and in the sub-acute LH test were mediated by activating both I1R and α2AR.


Depression Agmatine I1-imidazoline receptor α2-adrenergic receptor 



The work was supported by National Natural Science Foundation of China (81373385).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina
  2. 2.Program in Cellular and Molecular Medicine, Boston Children’s HospitalHarvard Medical SchoolBostonUSA

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