title: Behavioral and biochemical evaluation of sub-lethal inhalation exposure to VX in rats.
abstract: We evaluated the effects of low-level inhalation exposures (whole body, 60min duration) to the chemical warfare nerve agent VX (0.016, 0.15, 0.30 or 0.45mg/m(3)) in rats. The range of concentrations was approximately equivalent to 0.02-0.62 times 1.0 LC50. Biochemical effects were assessed by evaluating blood acetylcholinesterase (AChE) activity and by a regeneration assay that quantified the amount of VX (as the G analog) present in blood. Behavioral effects were assessed using a variable-interval 56-s schedule of reinforcement (VI56), in which rats were trained to press a lever to receive a food reward. VI56 training was established before exposure and evaluations continued after exposure. Additionally, after exposure, acquisition and maintenance of an eight-arm radial maze (RAM) task was evaluated in which rats learned to locate the four arms of the maze that presented a single food pellet reward. Behavioral assessments were conducted over approximately 3 months following exposure. Transient miosis was observed following exposure to all concentrations of VX and exposures to the 0.45mg/m(3) concentration also produced mild and temporary signs of toxicity (i.e., slight tremor and ataxia) in some subjects. All concentrations of VX also inhibited circulating AChE and the highest concentration inhibited AChE activity to less than 10% of pre-exposure values. Regenerated VX-G was found in red blood cell (RBC) and plasma blood fractions. In this respect, more VX-G was seen in plasma than RBC. Only small disruptions were observed on the VI56 or RAM following some VX exposures. In general, however, behavioral effects were minor and not clearly systematic. Taken together these results demonstrate that largely asymptomatic exposures to VX vapors in rats can produce substantial biochemical effects while having only minor performance effects on a previously learned behavioral task and on the acquisition of a new behavioral task.
authors.affiliation: Division of Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. raymond.genovese@us.army.mil
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Genovese
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Benton
authors.forename: Esther H
authors.initials: EH
authors.lastname: Lee
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Shippee
authors.forename: E Michael
authors.initials: EM
authors.lastname: Jakubowski
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000280:Administration, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002619:Chemical Warfare Agents / Q000494:pharmacology* / Q000633:toxicity; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D018782:Maze Learning / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000110:Acetylcholinesterase; D002619:Chemical Warfare Agents; D009946:Organothiophosphorus Compounds; C009680:VX-agent