PMID- 24819591 OWN - NLM STAT- MEDLINE DCOM- 20150306 LR - 20231110 IS - 1872-9738 (Electronic) IS - 0892-0362 (Print) IS - 0892-0362 (Linking) VI - 44 DP - 2014 Jul-Aug TI - Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats. PG - 18-29 LID - S0892-0362(14)00108-1 [pii] LID - 10.1016/j.ntt.2014.04.069 [doi] AB - Organophosphate (OP)-based chemicals are used worldwide for many purposes and they have likely saved millions of people from starvation and disease. However, due to their toxicity they can also pose a significant environmental risk. While considerable research has focused on the acute symptoms and long-term consequences of overtly toxic exposures to OPs, less attention has been given to the subject of repeated exposures to levels that are not associated with acute symptoms (subthreshold exposures). There is clinical evidence indicating that this type of OP exposure can lead to prolonged deficits in cognition; however only a few studies have addressed this issue prospectively in animal models. In this study, repeated subthreshold exposures to the OP nerve agent diisopropylfluorophosphate (DFP) were evaluated in a 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT and then injected subcutaneously with vehicle or DFP of 0.5mg/kg every other day for 30days. Behavioral testing occurred daily during the DFP-exposure period and throughout a 45day (OP-free) washout period. Compared to vehicle-treated controls, DFP-treated rats exhibited deficits in accuracy, increases in omissions and timeout responses during the OP exposure period, while no significant effects on premature responses, perseverative responses, or response latencies were noted. While the increase in timeout responses remained detectible during washout, all other DFP-related alterations in 5C-SRTT performance abated. When the demands of the task were increased by the presentation of variable intertrial intervals, premature responses were also elevated in DFP-treated rats during the washout period. These results indicate that repeated exposures to subthreshold doses of DFP lead to reversible impairments in sustained attention as well as persistent impairments of inhibitory response control in rats. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Terry, Alvin V Jr AU - Terry AV Jr AD - Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, United States; Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. Electronic address: aterry@gru.edu. FAU - Callahan, Patrick M AU - Callahan PM AD - Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, United States; Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. FAU - Beck, Wayne D AU - Beck WD AD - Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, United States. FAU - Vandenhuerk, Leah AU - Vandenhuerk L AD - Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. FAU - Sinha, Samantha AU - Sinha S AD - Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. FAU - Bouchard, Kristy AU - Bouchard K AD - Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. FAU - Schade, Rose AU - Schade R AD - Small Animal Behavior Core, Georgia Regents University, Augusta, GA 30912, United States. FAU - Waller, Jennifer L AU - Waller JL AD - Department of Biostatistics, Georgia Regents University, Augusta, GA 30912, United States. LA - eng GR - R01 ES012241/ES/NIEHS NIH HHS/United States GR - R01-ES012241/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140510 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Cholinesterase Inhibitors) RN - 12UHW9R67N (Isoflurophate) RN - EC 3.1.1.8 (Cholinesterases) SB - IM MH - Animals MH - Attention/*drug effects MH - Cholinesterase Inhibitors/administration & dosage/*toxicity MH - Cholinesterases/blood MH - *Inhibition, Psychological MH - Isoflurophate/administration & dosage/*toxicity MH - Male MH - Rats MH - Rats, Wistar MH - Reaction Time/drug effects PMC - PMC4099306 MID - NIHMS597169 OTO - NOTNLM OT - Cholinesterase inhibitor OT - Cognition OT - Memory OT - Nerve agent OT - Organophosphate OT - Pesticide COIS- Conflict of Interest Statement None of the authors of this manuscript have any financial, personal, or other conflicts of interest that could have inappropriately influenced the work described. EDAT- 2014/05/14 06:00 MHDA- 2015/03/07 06:00 PMCR- 2015/07/01 CRDT- 2014/05/14 06:00 PHST- 2013/09/20 00:00 [received] PHST- 2014/04/28 00:00 [revised] PHST- 2014/04/30 00:00 [accepted] PHST- 2014/05/14 06:00 [entrez] PHST- 2014/05/14 06:00 [pubmed] PHST- 2015/03/07 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - S0892-0362(14)00108-1 [pii] AID - 10.1016/j.ntt.2014.04.069 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2014 Jul-Aug;44:18-29. doi: 10.1016/j.ntt.2014.04.069. Epub 2014 May 10.