Neuronal Degeneration in the Cingulate Gyrus: NMDA Antagonists and Anticholinesterases
Abstract
The primary objective of these studies was to determine the neurotoxic risks of combining acetyloholinesterase inhibitors (AChEIs) with N-methyl-D-aspartate (NMDA) receptor antagonists. There is evidence that although NMDA receptor antagonists are considered neuroprotective against excess glutamate release during acute conditions, these same agents may also induce neurodegeneration in brain areas associated with attention and motivation; This neurodegeneration is exacerbated by muscarinic cholinergic agonists. Military personnel and civilians may be exposed to a wide array of cholinesterase inhibitors by pesticide exposure, chemical weapons deployment or prophylactic treatment. Exposure to these agents may elevate brain levels of acetyloholine (ACh), leading to increased muscarinic cholinergic stimulation. Individuals may be at risk of neuronal degeneration if they are co-exposed to a NMDA receptor antagonist, for example, cough suppressants, anticonvulsants, ethanol or the Alzheimer Disease agent, memantine. We approached this problem by using patch-clamp electrophysiology, behavioral assessment and histopathology to examine the effects NMDA receptor antagonists in animals co-exposed to AChET agents. We found that the AChET, PB is neuroprotective in some animals co-exposed to NMDA antagonists, but is lethal in others.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA421256
Entities
People
- Wilkie A. Wilson
Organizations
- Duke University