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The antidepressant-like action of metabotropic glutamate 7 receptor agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) is serotonin-dependent.
J Pharmacol Exp Ther. 2010 Sep 01; 334(3):1066-74.JP

Abstract

Behavioral studies show that modulation of the glutamatergic system might be an efficient way to achieve antidepressant activity. Among the group III metabotropic glutamate (mGlu) receptors, the mGlu7 receptor subtype seems to be the most promising target for potential antidepressants. It has been shown that a selective, allosteric mGlu7 receptor agonist, N,N'-bis (diphenylmethyl)-1,2-ethanediamine (AMN082), induced antidepressant-like action in behavioral tests in mice, although the mechanisms responsible for this action remained unknown. Here, we decided to investigate the possible role of the serotonergic system in the antidepressant-like activity of AMN082 in both the forced swim test (FST) in rats and the tail suspension test (TST) in mice. We found that AMN082 (1-10 mg/kg i.p.) induced a dose-dependent reduction in the immobility of rats and an increase in their swimming behavior, whereas there were not any changes in climbing behavior in the FST in rats. In the TST in mice we found that AMN082 (3 mg/kg i.p.) did not induce an antidepressant-like effect after depletion of serotonin (5-HT) with para-chlorophenylalanine. Moreover, we revealed that citalopram, but not reboxetine, when combined with AMN082 (all compounds used at low subeffective doses), induced a significant antidepressant-like effect in the TST. We also discovered that the 5-HT1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635) (0.1 mg/kg s.c.), but not the 5-HT2A/2C receptor antagonist ritanserin (0.5 mg/kg i.p.), blocked the antidepressant-like action of AMN082. Altogether, the results of our studies show that the antidepressant-like action of the mGlu7 receptor-positive modulator AMN082 depends on the activation of the serotonergic system.

Authors+Show Affiliations

Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nfpaluch@cyf-kr.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20562216

Citation

Pałucha-Poniewiera, Agnieszka, et al. "The Antidepressant-like Action of Metabotropic Glutamate 7 Receptor Agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) Is Serotonin-dependent." The Journal of Pharmacology and Experimental Therapeutics, vol. 334, no. 3, 2010, pp. 1066-74.
Pałucha-Poniewiera A, Brański P, Lenda T, et al. The antidepressant-like action of metabotropic glutamate 7 receptor agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) is serotonin-dependent. J Pharmacol Exp Ther. 2010;334(3):1066-74.
Pałucha-Poniewiera, A., Brański, P., Lenda, T., & Pilc, A. (2010). The antidepressant-like action of metabotropic glutamate 7 receptor agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) is serotonin-dependent. The Journal of Pharmacology and Experimental Therapeutics, 334(3), 1066-74. https://doi.org/10.1124/jpet.110.169730
Pałucha-Poniewiera A, et al. The Antidepressant-like Action of Metabotropic Glutamate 7 Receptor Agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) Is Serotonin-dependent. J Pharmacol Exp Ther. 2010 Sep 1;334(3):1066-74. PubMed PMID: 20562216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antidepressant-like action of metabotropic glutamate 7 receptor agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine (AMN082) is serotonin-dependent. AU - Pałucha-Poniewiera,Agnieszka, AU - Brański,Piotr, AU - Lenda,Tomasz, AU - Pilc,Andrzej, Y1 - 2010/06/18/ PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/9/24/medline SP - 1066 EP - 74 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 334 IS - 3 N2 - Behavioral studies show that modulation of the glutamatergic system might be an efficient way to achieve antidepressant activity. Among the group III metabotropic glutamate (mGlu) receptors, the mGlu7 receptor subtype seems to be the most promising target for potential antidepressants. It has been shown that a selective, allosteric mGlu7 receptor agonist, N,N'-bis (diphenylmethyl)-1,2-ethanediamine (AMN082), induced antidepressant-like action in behavioral tests in mice, although the mechanisms responsible for this action remained unknown. Here, we decided to investigate the possible role of the serotonergic system in the antidepressant-like activity of AMN082 in both the forced swim test (FST) in rats and the tail suspension test (TST) in mice. We found that AMN082 (1-10 mg/kg i.p.) induced a dose-dependent reduction in the immobility of rats and an increase in their swimming behavior, whereas there were not any changes in climbing behavior in the FST in rats. In the TST in mice we found that AMN082 (3 mg/kg i.p.) did not induce an antidepressant-like effect after depletion of serotonin (5-HT) with para-chlorophenylalanine. Moreover, we revealed that citalopram, but not reboxetine, when combined with AMN082 (all compounds used at low subeffective doses), induced a significant antidepressant-like effect in the TST. We also discovered that the 5-HT1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635) (0.1 mg/kg s.c.), but not the 5-HT2A/2C receptor antagonist ritanserin (0.5 mg/kg i.p.), blocked the antidepressant-like action of AMN082. Altogether, the results of our studies show that the antidepressant-like action of the mGlu7 receptor-positive modulator AMN082 depends on the activation of the serotonergic system. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20562216/The_antidepressant_like_action_of_metabotropic_glutamate_7_receptor_agonist_NN'_bis_diphenylmethyl__12_ethanediamine__AMN082__is_serotonin_dependent_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20562216 DB - PRIME DP - Unbound Medicine ER -