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.
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 microM)-induced depression of synaptic transmission; and 3) learning of the hidden platform version of the water maze by mice. BAY 36-7620 (10 microM) amplified LTP but, like the mGluR1 antagonists 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt, 10 microM) and 4-carboxyphenylglycine (4-CPG, 50 microM), diminished LTP at 1 microM. The mGluR5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP, 10 microM) had no effect. BAY 36-7620 (10 microM) 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 microM) or 4-CPG (100 microM). 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.
Schröder
U H
UH
Research Institute for Applied Neurosciences GmbH, Leipziger Str. 44, D-39120 Magdeburg, Germany. schroede@ifn-magdeburg.de
Müller
T
T
Schreiber
R
R
Stolle
A
A
Zuschratter
W
W
Balschun
D
D
Jork
R
R
Reymann
K G
KG
D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009281:Naphthalenes / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000172:deficiency; D009435:Synaptic Transmission / Q000187:drug effects*
C425484:BAY36-7620; D018691:Excitatory Amino Acid Antagonists; D009281:Naphthalenes; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1