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Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling.
Neuropharmacology. 2004 Sep; 47(3):342-50.N

Abstract

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic drugs including the involvement of group I metabotropic glutamate (mGlu) receptors. Given the recent discovery of a selective and brain penetrable mGlu5 receptor antagonists, the effect of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), i.e. the most potent mGlu5 antagonist, was evaluated in established models of anxiety after single or repeated administration. We also studied if the anxiolytic effect of MTEP is mediated by mechanism involving the GABA-benzodiazepine (BZD) receptor complex. Experiments were performed on male Wistar rats or male Albino Swiss mice. The anxiolytic-like effects of MTEP were tested in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. MTEP (0.3-3.0 mg/kg) induced anxiolytic-like effects in the conflict drinking test (after single and repeated administration) and in the elevated plus-maze test in rats. In the four-plate test in mice, it exerted anxiolytic activity at a dose of 20 mg/kg. MTEP had no effect on the locomotor activity of animals. The anxiolytic-like effect of MTEP was not changed by BZD antagonist flumazenil. Moreover, a synergistic interaction between non-effective doses of MTEP and diazepam was observed in the conflict drinking test. These data suggest that selective mGlu5 receptor antagonists mediated anxiolysis is not dependent on GABA-ergic system and that these agents may play a role in the therapy of anxiety.

Authors+Show Affiliations

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31343 Krakow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15275823

Citation

Klodzinska, Aleksandra, et al. "Anxiolytic-like Effects of MTEP, a Potent and Selective mGlu5 Receptor Agonist Does Not Involve GABA(A) Signaling." Neuropharmacology, vol. 47, no. 3, 2004, pp. 342-50.
Klodzinska A, Tatarczyńska E, Chojnacka-Wójcik E, et al. Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling. Neuropharmacology. 2004;47(3):342-50.
Klodzinska, A., Tatarczyńska, E., Chojnacka-Wójcik, E., Nowak, G., Cosford, N. D., & Pilc, A. (2004). Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling. Neuropharmacology, 47(3), 342-50.
Klodzinska A, et al. Anxiolytic-like Effects of MTEP, a Potent and Selective mGlu5 Receptor Agonist Does Not Involve GABA(A) Signaling. Neuropharmacology. 2004;47(3):342-50. PubMed PMID: 15275823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling. AU - Klodzinska,Aleksandra, AU - Tatarczyńska,Ewa, AU - Chojnacka-Wójcik,Ewa, AU - Nowak,Gabriel, AU - Cosford,Nicholas D P, AU - Pilc,Andrzej, PY - 2003/12/13/received PY - 2004/03/18/revised PY - 2004/04/22/accepted PY - 2004/7/28/pubmed PY - 2004/12/16/medline PY - 2004/7/28/entrez SP - 342 EP - 50 JF - Neuropharmacology JO - Neuropharmacology VL - 47 IS - 3 N2 - Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic drugs including the involvement of group I metabotropic glutamate (mGlu) receptors. Given the recent discovery of a selective and brain penetrable mGlu5 receptor antagonists, the effect of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), i.e. the most potent mGlu5 antagonist, was evaluated in established models of anxiety after single or repeated administration. We also studied if the anxiolytic effect of MTEP is mediated by mechanism involving the GABA-benzodiazepine (BZD) receptor complex. Experiments were performed on male Wistar rats or male Albino Swiss mice. The anxiolytic-like effects of MTEP were tested in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. MTEP (0.3-3.0 mg/kg) induced anxiolytic-like effects in the conflict drinking test (after single and repeated administration) and in the elevated plus-maze test in rats. In the four-plate test in mice, it exerted anxiolytic activity at a dose of 20 mg/kg. MTEP had no effect on the locomotor activity of animals. The anxiolytic-like effect of MTEP was not changed by BZD antagonist flumazenil. Moreover, a synergistic interaction between non-effective doses of MTEP and diazepam was observed in the conflict drinking test. These data suggest that selective mGlu5 receptor antagonists mediated anxiolysis is not dependent on GABA-ergic system and that these agents may play a role in the therapy of anxiety. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15275823/Anxiolytic_like_effects_of_MTEP_a_potent_and_selective_mGlu5_receptor_agonist_does_not_involve_GABA_A__signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390804001121 DB - PRIME DP - Unbound Medicine ER -