The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison.
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.
Gravius
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A
Preclinical R & D, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany.
Barberi
C
C
Schäfer
D
D
Schmidt
W J
WJ
Danysz
W
W
D000161:Acoustic Stimulation; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004597:Electroshock; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
C502015:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D015283:Citalopram; D016291:Dizocilpine Maleate; D012601:Scopolamine; D003975:Diazepam