The Effect of Acute and Chronic Treatment With Diisopropyl Fluorophosphate on Cholinesterase Activities of Some Tissues of the Rat

Abstract

Summary. Tlie activity of cliolincsti'mse was measured in brain cortex, basal ji;ui«Iia, liippofaiupiis, tliidamns, fiillii'uh', ccrt'hcliniu, niwhdla. liyiKitlialaiiuis, .spinal iDrd, irastrwiinuius inu.stU', atlrcnal glaml aiul retina at various times after treatment of rals with dii.Miprnp\l lluoroplinsphalt' alone or together with I,3-I)is{-l-hydro\yiiniu(unethyIp>rit!iniu[n) propuue dihroniide (C434).-After injection of ] m^. ihisopropyl Huorophosphate/ky. lK)tIy woij^lit intramuscularly in the leff the dioline.stcrase activity of neural tissue was decreased to 30-40% of control value.s and it increased to 7()-100?i of control values in 25 days. In each ease the rate of iiitrease of activity with time deereased tlironghotit this period, and was not changed signifitantly by eoneurrent treatment with C434. The proixirtional rate of increase in tlie cerebellum was signilitanlly greater than that in other neural tissue.The decrease in eholine.sterase activity of leg nniscle injected witli diisopropyl fluorophosphate was less marked in animals treated witli C4.34. The acti\ity in adrenals returned to eontrol values within 5 days and was 100-120? of control values for 5-10 days; tliesc-effects werc^ not altered by treatment with C434.

Toxicity of Soman after Repetitive Injection of Sublethal Doses in Rat

“…A common feature of adaptation to chronic organophosphate exposure is the low cholinesterase activity, which is maintained at a constant low level (10-30% of control) even if treatment is continued over a longer period (up to 60 days) (Brodeur & Dubois 1964;Glow et al 1966;Stavinoha et al 1969;Russel et al 1975). It is tempting to suggest that there is enough functional acetylcholinesterase present for the animals to survive or that the functional pool of acetylcholinesterase is preferentially recovered in these animals.…”

“…1952), demeton (Barnes & Denz 1954), disulfoton (Brodeur & Dubois 1964;Stavinoha et a/. 1969), D F P (Glow et a/. 1966;Russel et al, 1975) and paraoxon (Wecker e t a / .…”

Uses of double-pulse stimulation behaviorally to infer refractoriness, summation, convergence, and transmitter characteristics of hypothalamic reward systems.

“…Thus, a 1.0 mg/kg dose of DFP was used. Glow, Rose, and Richardson (1966) found that when the drug was given by an intramuscular route, it was necessary to administer this large a dose in order to reduce brain acetylchone concentration by 90%. At the end of the experiment, two of the rats were retested on DFP at a dose of .5 mg/kg im.…”

Effects on reinforced and nonreinforced responses of depressed and of elevated brain acetylcholine levels

“…The C434 protects AChE against DFP and reactivates phosphorylated AChE but does not pass the blood-brain barrier, thus attenuating peripheral actions of DFP without producing central effects or affecting behaviour . Data on AChE activity in nine brain areas 24 hr after this treatment showed a decrease to 30-40% of control values; 7 days after injection recovery to activity levels of 51% (cortex) to 89% (cerebellum) occurred (Glow, Rose, & Richardson, 1966). Previous research Russell et al, 1961) has shown that behavioural effects of decreased AChE activity appear when reduction is below a critical level at 40-45% normal activity.…”