title: 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.
authors.affiliation: Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. Raymond.Genovese@na.amedd.army.mil
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Genovese
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Benton
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Shippee
authors.forename: Edward M
authors.initials: EM
authors.lastname: Jakubowski
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Bonnell
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000187:drug effects / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D015877:Miosis / Q000139:chemically induced; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate