The potent non-competitive mGlu1 receptor antagonist BAY 36-7620 differentially affects synaptic plasticity in area cornu ammonis 1 of rat hippocampal slices and impairs acquisition in the water maze task in mice

• Published in: Neuroscience 2008-11, Vol.157 (2), p.385-395
• Main Authors: Schröder, U.H, Müller, T, Schreiber, R, Stolle, A, Zuschratter, W, Balschun, D, Jork, R, Reymann, K.G
• Format: Article
• Language: English
• Subjects: 3,5-dihydroxyphenylglycine; Analysis of Variance; Animals; BAY 36-7620; Biological and medical sciences; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampus - cytology; Hippocampus - drug effects; long-term depression; long-term potentiation; Male; Maze Learning - drug effects; metabotropic glutamate receptor; Mice; Mice, Knockout; Naphthalenes - pharmacology; Neurology; Neuronal Plasticity - drug effects; Patch-Clamp Techniques; rat hippocampal slice; Rats; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - deficiency; Synaptic Transmission - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.08.063

Abstract In this study we evaluated the effects of the novel, potent non-competitive metabotropic glutamate receptor (mGluR) 1 antagonist (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on (BAY 36-7620) on different types of synaptic plasticity in the hippocampal cornu ammonis (CA) 1-region and on hippocampus-dependent spatial learning. After having confirmed the presence of mGluR1 in the hippocampal CA1 region of our rat strain by confocal microscopy, we tested the effects of BAY 36-7620 on: 1) long-term potentiation (LTP) induced by weak and strong stimulation; 2) 3,5-dihydroxyphenylglycine (DHPG, 30 μM)-induced depression of synaptic transmission; and 3) learning of the hidden platform version of the water maze by mice. BAY 36-7620 (10 μM) amplified LTP but, like the mGluR1 antagonists 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt, 10 μM) and 4-carboxyphenylglycine (4-CPG, 50 μM), diminished LTP at 1 μM. The mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 10 μM) had no effect. BAY 36-7620 (10 μM) did not affect strong LTP. Thus, mGlu 1, but not mGlu 5, receptors modulate LTP elicited by weak stimulation in vitro . DHPG-induced depression of synaptic transmission was only marginally affected by BAY 36-7620 (1 μM) or 4-CPG (100 μM). In a mouse water maze study, BAY 36-7620 (10 mg/kg, i.v.) increased the escape latency and impaired water escape task acquisition during the first 4 days. Drug- and vehicle-treated groups showed comparable performance at day 5. Our data support a role for mGluR1 in LTP and in the acquisition of spatial memory.