Blockade of hippocampal long-term potentiation following soman pretreatment in the rat.
One of the most potent toxins known is the cholinesterase inhibitor, soman, which produces severe convulsions and cell loss in the central nervous system. In these experiments the effect of multiple low doses of soman on the acquisition and maintenance of long-term potentiation (LTP) was determined in rats. LTP is a form of synaptic plasticity that has been studied as a cellular substrate for learning and memory mechanisms. Under urethane anesthesia, electrodes were positioned in the dentate gyrus for recording evoked potentials before and after tetanic stimulation of the perforant path. LTP levels were greatly reduced in rats recovering from convulsion-inducing soman treatment. Rats exposed to similar amounts of soman, but not displaying convulsions, also displayed reduced levels of LTP. The responses recorded from these animals were highly variable, ranging from control levels of potentiation to no LTP. The variability could be attributed to some animals having convulsions that were not detected before surgery or to other interanimal differences in the degree of soman-induced toxicity. The long range goal of the experiments presented here is to develop a better rodent model for studying soman-induced functional changes in the CNS that can be detected prior to the gross morphological changes.
Armstrong
D L
DL
Division of Life Sciences, University of Texas at San Antonio 78249-0662, USA.
Osaka
T
T
Murphy
M R
MR
Kerenyi
S Z
SZ
Miller
S A
SA
Hartgraves
S L
SL
D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D018891:Dentate Gyrus / Q000187:drug effects / Q000648:ultrastructure; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D012999:Soman