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Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex
Carl Weitlauf1, John J Woodward
1Department of Neurosciences and Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Alcoholism, Clinical and Experimental Research
|March 18, 2008
Summary
Ethanol disrupts brain activity in alcoholics by inhibiting N-methyl-D-aspartate receptors (NMDARs) in the prefrontal cortex (PFC). This finding may explain alcohol-induced impulsivity and aid in developing addiction treatments.
Area of Science:
- Neuroscience
- Neuropharmacology
- Addiction Research
Background:
- Alcoholism is linked to prefrontal cortex (PFC) dysfunction, contributing to impulsive behavior.
- Understanding ethanol's effects on PFC neurons is crucial for treating alcohol addiction.
- Previous research showed ethanol inhibits persistent neuronal activity (up-states) in the medial PFC (mPFC).
Purpose of the Study:
- To investigate how ethanol affects glutamatergic and GABAergic components of persistent activity in mPFC neurons.
- To determine the specific receptor subtypes sensitive to ethanol's effects on neuronal activity.
Main Methods:
- Whole-cell patch clamp recordings were utilized.
- Electrically evoked and spontaneous excitatory and inhibitory postsynaptic currents were measured.
- The impact of varying ethanol concentrations on neuronal responses was assessed.
Main Results:
- Ethanol reversibly inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated EPSCs in deep-layer mPFC pyramidal neurons.
- Inhibition of NMDARs was significant at 22 mM ethanol (0.1% BAC).
- Ethanol did not affect AMPA-receptor mediated EPSCs or GABA-receptor mediated IPSCs/tonic currents, even at high concentrations.
Conclusions:
- NMDAR-mediated processes in the mPFC are particularly vulnerable to acute ethanol exposure.
- Ethanol's selective disruption of NMDARs may underlie impaired PFC function in alcoholism.
- These findings offer insights into the neurobiological mechanisms of alcohol addiction and loss of control.
