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Agonist action of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) in the amygdala
N B Keele1, V Arvanov, K Holmes
1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Abstract:
Glutamatergic excitatory postsynaptic potentials (EPSPs) in the basolateral amygdala (BLA) are reduced in amplitude following agonist activation of presynaptic metabotropic glutamate receptors (mGluR). In this study, the effect of a presumed mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), was investigated on the EPSP recorded intracellularly in BLA neurons. Superfusion of MCPG (500 microM) significantly reduced the amplitude of evoked EPSPs. In the presence of MCPG, postsynaptic responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA, 1 microM) were unaltered while responses to N-methyl-D-aspartate (NMDA, 3-5 microM) were potentiated. These data suggest that the MCPG-induced reduction of EPSP amplitude is due to a mGluR agonist action at a presynaptic mGluR 'autoreceptor'.
Insights
The metabotropic glutamate receptor antagonist MCPG unexpectedly reduced excitatory postsynaptic potentials (EPSPs) in the basolateral amygdala (BLA). This suggests MCPG acts as an agonist at presynaptic mGluRs, impacting BLA neuron activity.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- Glutamatergic excitatory postsynaptic potentials (EPSPs) in the basolateral amygdala (BLA) are modulated by presynaptic metabotropic glutamate receptors (mGluRs).
- Activation of presynaptic mGluRs typically leads to a reduction in EPSP amplitude.
Purpose of the Study:
- To investigate the effect of the presumed mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) on EPSPs in BLA neurons.
- To elucidate the mechanism behind MCPG's action on glutamatergic transmission in the BLA.
Main Methods:
- Intracellular recordings of EPSPs in BLA neurons.
- Application of MCPG, AMPA, and NMDA to superfused brain slices.
- Analysis of changes in EPSP amplitude and postsynaptic responses.
Main Results:
- Superfusion of MCPG (500 microM) significantly reduced the amplitude of evoked EPSPs in BLA neurons.
- Postsynaptic responses to AMPA (1 microM) remained unaltered in the presence of MCPG.
- Responses to NMDA (3-5 microM) were potentiated by MCPG.
Conclusions:
- The data suggest that MCPG acts as an agonist at presynaptic mGluR 'autoreceptors' rather than an antagonist.
- This agonist action of MCPG at presynaptic mGluRs mediates the observed reduction in EPSP amplitude.
- The findings highlight a complex pharmacological profile of MCPG in the BLA, impacting glutamatergic neurotransmission.