The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats

• Published in: Neuropharmacology Vol. 41; no. 1; pp. 1 - 7
• Main Authors: Schulz, Brigitte, Fendt, Markus, Gasparini, Fabrizio, Lingenhöhl, Kurt, Kuhn, Rainer, Koch, Michael
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2001; Elsevier
• Subjects: 2-methyl-6-(phenylethynyl)-pyridine; 6-Methyl-2-(phenylethynyl)pyridine; Acoustic startle response; Acoustic Stimulation; Anatomical correlates of behavior; Animals; Behavioral psychophysiology; Biological and medical sciences; Conditioning (Psychology) - drug effects; Electroshock; Excitatory Amino Acid Antagonists - pharmacology; Fear; Fear - drug effects; Fear - psychology; Fundamental and applied biological sciences. Psychology; Glutamatergic system (aspartate and other excitatory aminoacids); Habituation, Psychophysiologic - drug effects; Learning; Learning - drug effects; Male; Medical sciences; Memory; Memory - drug effects; Metabotropic glutamate receptors; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Prepulse inhibition; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Reflex, Startle - drug effects; Learning; Fear; Metabotropic glutamate receptors; Acoustic startle response; Memory; Prepulse inhibition; Rat; Rodentia; Oral administration; Instrumental conditioning; Glutamate receptor; Startle reflex; Biological activity; Habituation; Pyridine derivatives; Resistance; Vertebrata; Sensitivity; Mammalia; Acquisition process; Metabotropic receptor; Animal; Antagonist; Inhibition
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(01)00036-3

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.