Effects of Low-level Inhalation Exposure to Cyclosarin on Learned Behaviors in Sprague-Dawley Rats

Abstract

Behavioral and biochemical effects of low-level whole-body inhalation exposure to the chemical warfare nerve agent cyclosarin (GF) were evaluated. Sprague-Dawley rats were first trained on a variable-interval, 56-s (VI56) schedule of food reinforcement. The VI56 schedule specifies that a single lever press, following an average interval of 56 s, produces food reinforcement (i.e., a single food pellet). Subjects were then exposed to GF vapor at concentrations of 1.6-5.2 mg/m3, or air control, for 60 min. Following exposures, performance on the VI56 and acquisition and maintenance of a radial-arm maze (RAM) spatial memory task were evaluated during 55 test sessions over approximately 11 wk. GF exposures produced miosis in all subjects and other mild clinical signs of toxicity at the highest concentration. Convulsions were not observed in any subjects. GF exposures produced concentration-dependent decreases in acetylcholinesterase and butyrylcholinesterase activity. Additionally, blood assays revealed concentration-dependent levels of regenerated GF, thus verifying systemic exposure. The largest concentration of GF disrupted performance on the VI56 task. The deficit, however, resolved by the third postexposure test session. All subjects acquired, and maintained, performance on the RAM task, and no significant differences were seen as a result of GF exposure. No delayed effects from exposures were observed. These results demonstrate that, in rats, inhalation exposure to GF at levels below those producing convulsions and other severe clinical signs of toxicity may produce performance deficits on learned behaviors, but the deficits appear to not be persistent.

Neurological aspects of chemical terrorism

“…Some of these long‐term effects could be related to subconvulsive exposures to nerve agent. It does appear in animal studies that subtle transient cognitive and physiological effects may occur after nonconvulsive doses of nerve agents,17, 18 but there is not any definitive evidence to support this theory. Clearly, more work is needed on the effects of both acute and chronic exposures to low levels of OP nerve agents 19…”

Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

“…In general, responding was maintained during sessions occurring only a few hours after the BOP sessions. Previous studies have shown that operant behavior is a reasonably sensitive measure of performance and we have previously used such procedures to evaluate the effects of drugs, toxins and ischemic injury (Genovese, et al, 1988;Genovese, et al, 1992;Genovese, et al, 1993;Genovese, et al, 2006). Moreover, TBI, from a fluid percussion injury, has been shown to decrease responding on a food-maintained operant task (Gorman, et al, 1993).…”

Neurocognitive and Biomarker Evaluation of Combination mTBI from Blast Overpressure and Traumatic Stress

“…In general, responding was maintained during sessions occurring only a few hours after the BOP sessions. Previous studies have shown that operant behavior is a reasonably sensitive measure of performance and we have previously used such procedures to evaluate the effects of drugs, toxins and ischemic injury (Genovese, et al, 1988;Genovese, et al, 1992; 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 22 Genovese, et al, 1993;Genovese, et al, 2006). Moreover, TBI, from a fluid percussion injury, has been shown to decrease responding on a food-maintained operant task (Gorman, et al, 1993).…”