title: Effects of sarin on the operant behavior of guinea pigs.
abstract: The present study evaluated the dose-response effects of subacute exposure to sublethal doses of the organophosphorus (OP) chemical warfare nerve agent (CWNA) sarin (GB) on the operant behavior of guinea pigs. Dietary restricted guinea pigs, trained to respond for food under a progressive ratio (PR) schedule of reinforcement, were injected five times per week (Monday-Friday) for 2 weeks with fractions (0.1, 0.2, and 0.4) of the established LD(50) of GB (42 microg/kg). Changes in body weight, whole blood (WB) acetylcholinesterase (AChE) levels, and operant performances were monitored over the 2 weeks of GB exposure and for an additional 2 weeks following the termination of exposures. There were dose-related changes in body weight and WB AChE levels throughout the exposure and post-exposure periods. Several parameters of PR performance were disrupted during exposure to 0.4 LD50 GB, however, concurrent weight loss indicated the presence of overt toxicity. PR performance recovered following the termination of exposures. Lower doses (0.1 and 0.2 LD50) of GB failed to produce reliable effects on operant performance during the exposure period. Overall responding decreased during exposure to 0.4 LD50 GB, resulting in reduced response rates and break points. The decrease in overall response rates was attributed to an increase in pausing since there was no decrease in running rate. Motor effects of 0.4 LD50 GB were evident as an increase in the proportion of lever press durations > or = 1.0 s. In the present study, doses of GB lower than 0.4 LD50 produced no marked alteration of operant performance in guinea pigs, although WB AChE levels were maximally inhibited to 20% of control.
authors.affiliation: Drug Assessment Division, US Army Medical Research Institute of Chemical Defense, MCMR-UV-DA, Aberdeen Proving Ground, MD 21010-5400, USA. Jeffrey.Langston@us.army.mil
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Langston
authors.forename: Angela L
authors.initials: AL
authors.lastname: Adkins
authors.forename: Anita V
authors.initials: AV
authors.lastname: Moran
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rockwood
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Deford
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D012524:Sarin / Q000494:pharmacology*
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D012524:Sarin