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The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in
B Schulz1, M Fendt, F Gasparini
1Animal Physiology, University of Tübingen, Tübingen, Germany.
Abstract:
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.
Insights
Group I metabotropic glutamate receptor 5 (mGluR5) antagonists, like MPEP, impair fear acquisition and expression in rats. This suggests mGluR5 is crucial for fear conditioning and may have anxiolytic potential at higher doses.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- Glutamate receptors are vital for learning and memory, particularly fear-related processes.
- Group I metabotropic glutamate receptors (mGluR5) involvement in fear conditioning remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of mGluR5 in the acquisition and retrieval of conditioned fear in a rat model.
- To assess the effects of the selective mGluR5 antagonist MPEP on fear conditioning.
Main Methods:
- Rats were trained using the fear-potentiated startle paradigm.
- The mGluR5 antagonist MPEP was administered systemically before acquisition or expression phases.
- Baseline startle, habituation, sensitization, and prepulse inhibition were measured.
Main Results:
- MPEP dose-dependently inhibited fear acquisition and expression.
- MPEP did not affect baseline startle, habituation, sensitization, or prepulse inhibition.
- Diazepam, a benzodiazepine anxiolytic, also blocked fear acquisition and expression.
Conclusions:
- mGluR5 plays a critical role in the regulation of fear conditioning.
- MPEP may possess anxiolytic properties at higher doses, warranting further investigation.