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mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition.
Neuropharmacology. 2005 Jul; 49(1):73-85.N

Abstract

Hypoglutamatergic theory of schizophrenia is substantiated by observation that high affinity uncompetitive antagonists of NMDA receptors such as PCP can induce psychotic symptoms in humans. Recently, metabotropic glutamate receptors of the mGluR5 type have also been discussed as possible players in this disease. However, less is known about the potential contribution of mGluR1 in schizophrenia. Therefore, the aim of the present study was to compare the effect of selective mGluR1 antagonist EMQMCM, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist (MTEP ([(2-methyl-1, 3-thiazol-4-yl) ethynyl] pyridine) either alone or in combination with (+)MK-801 in a prepulse inhibition (PPI) model and locomotor activity tests. Additionally, the effect of both mGluR1 and mGluR5 antagonists on (+)MK-801-evoked ataxia was tested. In contrast to (+)MK-801, which induced disruption of PPI, neither MTEP (1.25-5 mg/kg) nor EMQMCM (0.5-4 mg/kg) altered the PPI. However, MTEP, but not EMQMCM, enhanced disruption of PPI induced by (+)MK-801. Although neither mGluR1 nor mGluR5 antagonists given alone changed locomotor activity of rats, MTEP at 5 mg/kg potentiated the effect of (+)MK-801 while EMQMCM (up to 4 mg/kg) turned out to be ineffective. On the other hand, EMQMCM, but not MTEP, enhanced ataxia evoked by MK-801. The present results demonstrate that blockade of mGluR1 and mGluR5 evokes different effects on behavior induced by NMDA receptor antagonists.

Authors+Show Affiliations

Pietraszek M
Preclinical R&D, Merz Pharmaceuticals, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.
Gravius A
No affiliation info available
Schäfer D
No affiliation info available
Weil T
No affiliation info available
Trifanova D
No affiliation info available
Danysz W
No affiliation info available

MeSH

Acoustic StimulationAnalysis of VarianceAnimalsBehavior, AnimalDizocilpine MaleateDose-Response Relationship, DrugDose-Response Relationship, RadiationDrug CombinationsDrug InteractionsExcitatory Amino Acid AntagonistsMaleMotor ActivityNeural InhibitionPyridinesQuinolinesRatsRats, Sprague-DawleyReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateReflex, StartleRotarod Performance TestThiazolesTime Factors

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15992582

Citation

Pietraszek, M, et al. "MGluR5, but Not mGluR1, Antagonist Modifies MK-801-induced Locomotor Activity and Deficit of Prepulse Inhibition." Neuropharmacology, vol. 49, no. 1, 2005, pp. 73-85.
Pietraszek M, Gravius A, Schäfer D, et al. MGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition. Neuropharmacology. 2005;49(1):73-85.
Pietraszek, M., Gravius, A., Schäfer, D., Weil, T., Trifanova, D., & Danysz, W. (2005). MGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition. Neuropharmacology, 49(1), 73-85.
Pietraszek M, et al. MGluR5, but Not mGluR1, Antagonist Modifies MK-801-induced Locomotor Activity and Deficit of Prepulse Inhibition. Neuropharmacology. 2005;49(1):73-85. PubMed PMID: 15992582.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition. AU - Pietraszek,M, AU - Gravius,A, AU - Schäfer,D, AU - Weil,T, AU - Trifanova,D, AU - Danysz,W, Y1 - 2005/03/31/ PY - 2004/12/02/received PY - 2005/01/25/revised PY - 2005/01/31/accepted PY - 2005/7/5/pubmed PY - 2005/12/13/medline PY - 2005/7/5/entrez SP - 73 EP - 85 JF - Neuropharmacology JO - Neuropharmacology VL - 49 IS - 1 N2 - Hypoglutamatergic theory of schizophrenia is substantiated by observation that high affinity uncompetitive antagonists of NMDA receptors such as PCP can induce psychotic symptoms in humans. Recently, metabotropic glutamate receptors of the mGluR5 type have also been discussed as possible players in this disease. However, less is known about the potential contribution of mGluR1 in schizophrenia. Therefore, the aim of the present study was to compare the effect of selective mGluR1 antagonist EMQMCM, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist (MTEP ([(2-methyl-1, 3-thiazol-4-yl) ethynyl] pyridine) either alone or in combination with (+)MK-801 in a prepulse inhibition (PPI) model and locomotor activity tests. Additionally, the effect of both mGluR1 and mGluR5 antagonists on (+)MK-801-evoked ataxia was tested. In contrast to (+)MK-801, which induced disruption of PPI, neither MTEP (1.25-5 mg/kg) nor EMQMCM (0.5-4 mg/kg) altered the PPI. However, MTEP, but not EMQMCM, enhanced disruption of PPI induced by (+)MK-801. Although neither mGluR1 nor mGluR5 antagonists given alone changed locomotor activity of rats, MTEP at 5 mg/kg potentiated the effect of (+)MK-801 while EMQMCM (up to 4 mg/kg) turned out to be ineffective. On the other hand, EMQMCM, but not MTEP, enhanced ataxia evoked by MK-801. The present results demonstrate that blockade of mGluR1 and mGluR5 evokes different effects on behavior induced by NMDA receptor antagonists. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15992582/mGluR5_but_not_mGluR1_antagonist_modifies_MK_801_induced_locomotor_activity_and_deficit_of_prepulse_inhibition_ DB - PRIME DP - Unbound Medicine ER -