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Abstract:
This report describes studies on organophosphorus (OP) inhibitors of acetylcholinesterase (AChE) in the mammalian spinal cord in which the mechanism and site of action of the OPs on synaptic transmission were studied with selective agonists and antagonists of putative central neurotransmitters. Spinal cords isolated from neonatal rats 5- to 9-days old were hemisected and placed in experimental chambers. Electrodes attached to dorsal and ventral root pairs recorded the monosynaptic (MSR) and polysynaptic reflexes (PSR). The roles of N- methyl-D-aspartate (NMDA) and non-NMDA receptors in the generation of MSRs and PSRs and in the action of AChE inhibitors were examined. Utilizing specific receptor inhibitors it was found that the AChE inhibitors caused depression through muscarinic, not nicotinic receptors, that oximes antagonize AChE inhibitors by virtue of their anticholinergic actions, and not regeneration of ChE and that thyrotropin releasing hormone can effectively reverse the depression of reflex activity. The facilitation caused by the AChE inhibitors was found to be caused by a block of bicuculline-sensitive inhibition. In addition, it was found that NMDA and non-NMDA receptors are present at synapses between the dorsal root afferent neuron and the excitatory interneuron in the PSR and between the dorsal root afferent neuron and motoneuron of the MSR. Compounds: Sarin, Organophosphorus; Spinal; CW Agents; Acetylcholinesterase Inhibitors; Physostigmine; Diisopropylphosphorofluoridate; Soman; Tabun; NMDA; Receptors; RAI.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Final rept. 1 Feb 86-30 Sep 89 |
| Pages: |
79 |
| Report Date: |
22 NOV 91 |
| Contract Number: |
DAMD17-86-C-6030 |
| Report Number: |
A496252 |
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