Cholinergic systems influence local cerebral glucose use in specific anatomical areas: diisopropyl phosphorofluoridate versus soman.
The organophosphates, diisopropyl phosphorofluoridate and soman have a common mechanism of action (inhibition of acetylcholinesterase), but result in very different behavioral responses in the rat. Soman rapidly produced persistent tonic convulsions whereas diisopropyl phosphorofluoridate only infrequently produced transient convulsive-like activity. Soman increased local cerebral glucose use in most of the cortex, striato-pallido-nigral pathway, limbic system and in specific thalamic nuclei whereas diisopropyl phosphorofluoridate increased glucose use in a limited fashion, primarily in the dorsal striato-pallido-nigral pathway. When diazepam blocked soman-induced convulsions, the pattern of glucose use was strikingly similar to that caused by diisopropyl phosphorofluoridate. Soman or diisopropyl phosphorofluoridate depressed local cerebral glucose use in rats pretreated with the antidotal mixture of trimedoxime, atropine and benactyzine (muscarinic antagonists). Also, this antidotal mixture blocked the increased glucose use in the dorsal striato-pallido-nigral system produced by either acetylcholinesterase inhibitor, indicating that muscarinic receptors mediate the excitation of this pathway. Both diisopropyl phosphorofluoridate and soman activate the striato-pallido-nigral pathway but soman also causes spread of activity producing overt motor convulsions. Possible explanations for this difference in response to the organophosphates are differential responses in cholinergic actions within specific brain regions or some non-cholinergic action of soman.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001535:Benactyzine / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007531:Isoflurophate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014289:Trimedoxime / Q000494:pharmacology
D007531:Isoflurophate; D014289:Trimedoxime; D001535:Benactyzine; D001285:Atropine; D012999:Soman; D005947:Glucose