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Glutamate receptor changes in brain synaptic membranes from human alcoholics
E K Michaelis1, W J Freed, N Galton
1Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
Neurochemical Research
|November 1, 1990
Summary
Chronic alcoholism alters glutamate receptor binding sites in the human hippocampus. Alcoholics show increased glutamate binding and altered N-methyl-D-aspartate (NMDA) receptor characteristics, suggesting neurobiological changes.
Area of Science:
- Neuroscience
- Neuropharmacology
- Addiction Research
Background:
- Glutamate receptors play a critical role in synaptic plasticity and neurotransmission.
- Alcoholism is associated with significant neurobiological alterations, but specific changes in hippocampal glutamate receptor binding remain unclear.
Purpose of the Study:
- To investigate alterations in glutamate binding sites within the hippocampus of human alcoholics compared to non-alcoholics.
- To characterize the specific changes in N-methyl-D-aspartate (NMDA) receptor subtype binding.
Main Methods:
- Human hippocampal tissue from deceased alcoholics and non-alcoholics was used.
- Synaptic membranes were isolated and analyzed for L-[3H]glutamate and [3H]CPP binding.
- Pharmacological characteristics of receptor binding sites were determined.
Main Results:
- Alcoholic brains exhibited a significantly higher density of L-[3H]glutamate binding sites in the hippocampus.
- A subpopulation of higher-affinity L-glutamate binding sites was identified in alcoholics.
- [3H]CPP binding revealed a 3-fold higher affinity but 3-fold lower capacity at NMDA receptors in alcoholics.
Conclusions:
- Chronic alcoholism leads to significant alterations in hippocampal glutamate receptor density and affinity.
- Changes in both overall glutamate binding and specific NMDA receptor characteristics are observed in alcoholics.
- These findings suggest that altered glutamatergic neurotransmission may contribute to the neurobiological consequences of alcoholism.