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The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison.
Neuropharmacology. 2006 Dec; 51(7-8):1146-55.N

Abstract

Glutamatergic neurotransmission in the CNS plays a predominant role in learning and memory. While NMDA receptors have been extensively studied, less is known about the involvement of group I metabotropic glutamate receptors in this area. The purpose of the present study was to evaluate the contribution of mGluR1 and mGluR5 to both acquisition and expression of behaviours in contextual and auditory fear conditioning models. The effects of both receptor types were tested using selective antagonists: (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) for mGluR1, and [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) for mGluR5. Their effects on acquisition were compared to those of the NMDA receptor antagonist (+)MK-801, and the unselective muscarinic antagonist scopolamine, while diazepam and citalopram served as reference compounds in the expression experiments. EMQMCM (1.25 to 5mg/kg) impaired acquisition of contextual fear conditioning (CFC), but not auditory fear conditioning (AFC). Similarly, administration of MTEP during the acquisition phase impaired learning in CFC at doses of 2.5 to 10mg/kg, but was ineffective in AFC. When given before the retention test, both EMQMCM (1 and 3mg/kg) and MTEP (3mg/kg) impaired expression of CFC. In contrast, MTEP (2.5 and 5mg/kg) blocked the expression of AFC, while EMQMCM was ineffective. In conclusion, group I mGlu receptors are shown to be involved in the acquisition of hippocampus-dependent CFC, but not hippocampus-independent AFC. Unlike mGluR5, mGluR1 does not seem be involved in expression of AFC.

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Authors+Show Affiliations

Gravius A
Preclinical R & D, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.
Barberi C
No affiliation info available
Schäfer D
No affiliation info available
Schmidt WJ
No affiliation info available
Danysz W
No affiliation info available

MeSH

Acoustic StimulationAnimalsAvoidance LearningCitalopramConditioning, ClassicalDiazepamDizocilpine MaleateElectroshockExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsFearFreezing Reaction, CatalepticHippocampusLong-Term PotentiationMalePyridinesQuinolinesRatsRats, Sprague-DawleyReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateScopolamineThiazoles

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16905160

Citation

Gravius, A, et al. "The Role of Group I Metabotropic Glutamate Receptors in Acquisition and Expression of Contextual and Auditory Fear Conditioning in Rats - a Comparison." Neuropharmacology, vol. 51, no. 7-8, 2006, pp. 1146-55.
Gravius A, Barberi C, Schäfer D, et al. The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison. Neuropharmacology. 2006;51(7-8):1146-55.
Gravius, A., Barberi, C., Schäfer, D., Schmidt, W. J., & Danysz, W. (2006). The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison. Neuropharmacology, 51(7-8), 1146-55.
Gravius A, et al. The Role of Group I Metabotropic Glutamate Receptors in Acquisition and Expression of Contextual and Auditory Fear Conditioning in Rats - a Comparison. Neuropharmacology. 2006;51(7-8):1146-55. PubMed PMID: 16905160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison. AU - Gravius,A, AU - Barberi,C, AU - Schäfer,D, AU - Schmidt,W J, AU - Danysz,W, Y1 - 2006/08/14/ PY - 2006/05/31/received PY - 2006/07/04/revised PY - 2006/07/07/accepted PY - 2006/8/15/pubmed PY - 2007/3/10/medline PY - 2006/8/15/entrez SP - 1146 EP - 55 JF - Neuropharmacology JO - Neuropharmacology VL - 51 IS - 7-8 N2 - Glutamatergic neurotransmission in the CNS plays a predominant role in learning and memory. While NMDA receptors have been extensively studied, less is known about the involvement of group I metabotropic glutamate receptors in this area. The purpose of the present study was to evaluate the contribution of mGluR1 and mGluR5 to both acquisition and expression of behaviours in contextual and auditory fear conditioning models. The effects of both receptor types were tested using selective antagonists: (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) for mGluR1, and [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) for mGluR5. Their effects on acquisition were compared to those of the NMDA receptor antagonist (+)MK-801, and the unselective muscarinic antagonist scopolamine, while diazepam and citalopram served as reference compounds in the expression experiments. EMQMCM (1.25 to 5mg/kg) impaired acquisition of contextual fear conditioning (CFC), but not auditory fear conditioning (AFC). Similarly, administration of MTEP during the acquisition phase impaired learning in CFC at doses of 2.5 to 10mg/kg, but was ineffective in AFC. When given before the retention test, both EMQMCM (1 and 3mg/kg) and MTEP (3mg/kg) impaired expression of CFC. In contrast, MTEP (2.5 and 5mg/kg) blocked the expression of AFC, while EMQMCM was ineffective. In conclusion, group I mGlu receptors are shown to be involved in the acquisition of hippocampus-dependent CFC, but not hippocampus-independent AFC. Unlike mGluR5, mGluR1 does not seem be involved in expression of AFC. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/16905160/The_role_of_group_I_metabotropic_glutamate_receptors_in_acquisition_and_expression_of_contextual_and_auditory_fear_conditioning_in_rats___a_comparison_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00215-2 DB - PRIME DP - Unbound Medicine ER -