The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison.

Full 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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Author information

Author/s: Gravius, A (A); Barberi, C (C); Schäfer, D (D); Schmidt, W J (WJ); Danysz, W (W);

Affiliation: Preclinical R & D, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.

Journal and publication information

Publication Type: Journal Article

Journal: Neuropharmacology (Neuropharmacology), published in England. (Language: eng)

Reference: 2006-Dec; vol 51 (issue 7-8) : pp 1146-55

Dates: Created 2006/11/19; Completed 2007/03/09;

PMID: 16905160, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acoustic Stimulation
Animals
Avoidance Learning - drug effects; physiology
Citalopram - pharmacology
Conditioning, Classical - drug effects; physiology
Diazepam - pharmacology
Dizocilpine Maleate - pharmacology
Electroshock
Excitatory Amino Acid Agonists - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Fear - drug effects; physiology

Freezing Reaction, Cataleptic - drug effects; physiology
Hippocampus - drug effects; physiology
Long-Term Potentiation - drug effects; physiology
Male
Pyridines - pharmacology
Quinolines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate - drug effects; physiology
Scopolamine - pharmacology
Thiazoles - pharmacology

Associated Chemicals: (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate (0) ; 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (0) ; Excitatory Amino Acid Agonists (0) ; Excitatory Amino Acid Antagonists (0) ; Pyridines (0) ; Quinolines (0) ; Receptors, Metabotropic Glutamate (0) ; Thiazoles (0) ; metabotropic glutamate receptor 5 (0) ; metabotropic glutamate receptor type 1 (0) ; Diazepam (439-14-5) ; Scopolamine (51-34-3) ; Citalopram (59729-33-8) ; Dizocilpine Maleate (77086-22-7)

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