Abstract: This report describes continued studies on organophosphorus (OP) inhibitors of acetylcholinesterase (AChE) in the mammalian spinal cord. The mechanism and site of action of the potentiation and/or depression of synaptic transmission by the OPs are being revealed with the use of selective agonists and antagonists of putative neurotransmitters. The spinal cords were isolated from neonatal rats 5- to 9-days old, hemisected, and placed in experimental chambers. Electrodes were attached to dorsal and ventral root pairs, and recordings of the monosynaptic reflex (MSR) were made from ventral roots under varying stimulation and recording paradigms to examine the actions of these agents. The ability of pralidoxime, trimedoxime or TMB-4, and diethyxime to reverse sarin-induced depression of the MSR in the isolated spinal cord from neonatal rats was examined. The reversal of sarin-induced depression was not accompanied by a regeneration of AChE activity in the spinal cord, suggesting that the reversal of sarin-induced depression of synaptic transmission in the spina cord by these oximes was unrelated to an effect on AChE or the accumulation of acetylcholine. It is more likely that the reversal resulted from blockade of cholinergic (muscarinic) receptors in the spinal cord.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Feb 88-31 Jan 89 |
| Pages: |
31 |
| Report Date: |
22 AUG 90 |
| Contract Number: |
DAMD17-86-C-6030 |
| Report Number: |
A680232 |
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