Evidence that alterations in gamma-aminobutyric acid and acetylcholine in rat striata and cerebella are not related to soman-induced convulsions.
Many reports have suggested that gamma-aminobutyric acid (GABA) may play a role in organophosphate-induced convulsions. The balance between GABA and acetylcholine (ACh) in the brain also has been suggested by some investigators to be related to brain excitability. We examined these questions by studying the levels of GABA and ACh and the ratios of GABA to ACh in rat striata and cerebella (two major motor control areas in the CNS) after the administration of soman, an organophosphate acetylcholinesterase inhibitor also known as nerve gas. Male Sprague-Dawley rats weighing 250-300 g were injected subcutaneously with three different doses of soman: a subconvulsive dose of 40 micrograms/kg (approximately 30% of the ED50 for convulsions in rats), a convulsive dose of 120 micrograms/kg (approximately one ED50 for convulsions), and a higher convulsive dose of 150 micrograms/kg (approximately 120% of the ED50 for convulsions). The incidence and severity of convulsions were monitored in individual rats until they were sacrificed by focused microwave irradiation of the head at the following time points after soman administration: 4 min, a time prior to the onset of convulsions; 10 min, the time of onset of convulsions; 1 h, the time of peak convulsive activity; and 6 h, a time at which rats were recovering from convulsions. Results showed that in rat striata and cerebella, neither changes in levels of GABA and ACh nor changes in ratios of GABA to ACh were related to soman-induced convulsions, i.e., none of the changes in either levels or ratios of these two neurotransmitters were related to the initiation of, maintenance of, or recovery from soman-induced convulsions.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Ueno
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Hoskins
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012999:Soman / Q000494:pharmacology / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D012999:Soman; D000109:Acetylcholine