The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats.
Glutamate receptors play an essential role in fear-related learning and memory. The present study was designed to assess the role of the group I metabotropic glutamate receptor (mGluR) subtype 5 in the acquisition and retrieval of conditioned fear in rats. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) was applied systemically (0.0, 0.3, 3.0, 30.0 mg/kg per os) 60 min before the acquisition training and before the expression of conditioned fear, respectively, in the fear-potentiated startle paradigm. MPEP dose-dependently blocked the acquisition of fear. This effect was not due to state-dependent learning. MPEP also prevented the expression of fear at a dose of 30.0 mg/kg. As a positive control for these effects, we showed that the benzodiazepine anxiolytic compound diazepam (1.25 mg/kg intraperitoneally) also blocked acquisition and expression of fear potentiated startle. MPEP did not affect the baseline startle magnitude, short-term habituation of startle, sensitisation of startle by footshocks or prepulse inhibition of startle. These data indicate a crucial role for mGluR5 in the regulation of fear conditioning. In the highest dose MPEP might exert anxiolytic properties.
Schulz
B
B
Animal Physiology, University of Tübingen, Tübingen, Germany.
Fendt
M
M
Gasparini
F
F
Lingenhöhl
K
K
Kuhn
R
R
Koch
M
M
D000161:Acoustic Stimulation; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine