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Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests.
Eur Neuropsychopharmacol. 2007 Feb; 17(3):172-9.EN

Abstract

Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor antagonists exert antidepressant-like effects in a variety of experimental paradigms, but their therapeutic application is limited by undesired side effects. In contrast, agents that reduce glutamatergic tone by blocking type I metabotropic glutamate receptors have been suggested to have more a favorable side-effect profile. The present study aimed to compare the effects of mGluR1 antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two behavioral screening assays commonly used to assess antidepressant-like activity. In the modified forced swim test in rats, imipramine (used as a positive control) decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg). In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25 mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was not affected by treatments. The present study therefore suggests that acute blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in behavioral despair tests in rats and mice.

Authors+Show Affiliations

Institute of Pharmacology, Pavlov Medical University, St Petersburg, Russia. beloiz@spmu.rssi.ruNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16630709

Citation

Belozertseva, I V., et al. "Antidepressant-like Effects of mGluR1 and mGluR5 Antagonists in the Rat Forced Swim and the Mouse Tail Suspension Tests." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 17, no. 3, 2007, pp. 172-9.
Belozertseva IV, Kos T, Popik P, et al. Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests. Eur Neuropsychopharmacol. 2007;17(3):172-9.
Belozertseva, I. V., Kos, T., Popik, P., Danysz, W., & Bespalov, A. Y. (2007). Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 17(3), 172-9.
Belozertseva IV, et al. Antidepressant-like Effects of mGluR1 and mGluR5 Antagonists in the Rat Forced Swim and the Mouse Tail Suspension Tests. Eur Neuropsychopharmacol. 2007;17(3):172-9. PubMed PMID: 16630709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests. AU - Belozertseva,I V, AU - Kos,T, AU - Popik,P, AU - Danysz,W, AU - Bespalov,A Y, Y1 - 2006/04/21/ PY - 2005/09/07/received PY - 2006/02/04/revised PY - 2006/03/07/accepted PY - 2006/4/25/pubmed PY - 2007/2/27/medline PY - 2006/4/25/entrez SP - 172 EP - 9 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 17 IS - 3 N2 - Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor antagonists exert antidepressant-like effects in a variety of experimental paradigms, but their therapeutic application is limited by undesired side effects. In contrast, agents that reduce glutamatergic tone by blocking type I metabotropic glutamate receptors have been suggested to have more a favorable side-effect profile. The present study aimed to compare the effects of mGluR1 antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two behavioral screening assays commonly used to assess antidepressant-like activity. In the modified forced swim test in rats, imipramine (used as a positive control) decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg). In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25 mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was not affected by treatments. The present study therefore suggests that acute blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in behavioral despair tests in rats and mice. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/16630709/Antidepressant_like_effects_of_mGluR1_and_mGluR5_antagonists_in_the_rat_forced_swim_and_the_mouse_tail_suspension_tests_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(06)00049-6 DB - PRIME DP - Unbound Medicine ER -