title: Postnatal diisopropylfluorophosphate enhances conditioned vigilance in adult BALB/c and C57BL/6 mice and alters expression of acetylcholinesterase splice variants.
abstract: The long-term effects of postnatal exposure to an organophosphate substance diisopropylfluorophosphate (DFP) were examined on fear conditioning in adult mice. Immediate and long-term changes in the expression of synaptic acetylcholinesterase (AChE-S) and readthrough acetylcholinesterase (AChE-R) transcripts were explored, in view of reports relating expression of these splice variants to stress and anxiety. BALB/c and C57BL/6 mice were injected daily, on postnatal days 4-10, with 1 mg/kg of DFP or saline and tested as adults for cued and contextual freezing and scanning. Real-time PCR was used to investigate expression of the rare AChE-R and AChE-S mRNA postnatally and in fear-conditioned adults. DFP-pretreated male mice showed increased conditioned cued scanning and both male and female DFP-treated mice showed enhanced contextual scanning. DFP abolished the stress-induced increase in AChE transcript expression in BALB/c but not in C57BL/6 mice. A significant correlation was found between expression of AChE-S and AChE-R transcripts in the hippocampus and scanning behavior, but this was apparently unrelated to DFP treatment. The enhanced conditioned scanning in adults, following postnatal exposure to DFP, suggests long-term effects on the risk for anxiety disorders. The altered expression of AChE splice variant transcripts in the two strains did not account for the behavioral deficits, which were observed in both BALB/c and C57BL/6 strains.
authors.affiliation: aDepartment of Psychology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva bTalpiot Medical Leadership Program, Department of Neurology, Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Oriel
authors.forename: Amir
authors.initials: A
authors.lastname: Dori
authors.forename: Ora
authors.initials: O
authors.lastname: Kofman
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000367:Age Factors; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D005260:Female; D007531:Isoflurophate / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D013045:Species Specificity; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D020033:Protein Isoforms; D012333:RNA, Messenger; D007531:Isoflurophate; D000110:Acetylcholinesterase