title: Two cholinesterase inhibitors trigger dissimilar effects on behavior and body weight in C57BL/6 mice: The case of chlorpyrifos and rivastigmine.
abstract: Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice. The animals were daily fed either a standard, a CPF- (5mg/kg body weight) or a rivastigmine-supplemented diet (1 or 2mg/kg body weight) for 8 weeks. After the treatment, we established an 8-week washout period to assess recovery. ChE enzyme activity, biomarkers, physical effects, and behavioral alterations were evaluated at different time points during the exposure and after the washout period. Both rivastigmine doses induced a time-dependent weight increase. CPF and rivastigmine inhibited brain acetylcholinesterase following an isoform-specific pattern. As for behavioral assessment, CPF negatively modulated learning strategies and impaired memory in a Barnes maze task at the end of the exposure. On the other hand, the low dose of rivastigmine improved memory recall at the end of the washout period in a Morris water maze. Indeed, our results endorse the positive effects of low doses of rivastigmine following a drug-free period in young mice. Therefore, doses and periodicity of treatment to improve cognition in elderly people upon rivastigmine administration should be revised.
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Pia
authors.initials: P
authors.lastname: Basaure
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Fiona
authors.initials: F
authors.lastname: Peris-Sampedro
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Cabré
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Psychology Department, Brooklyn College, City University of New York, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Reverte
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain. Electronic address: mariateresa.colomina@urv.cat.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Colomina
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D004390:Chlorpyrifos / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D000068836:Rivastigmine / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D004390:Chlorpyrifos; D000068836:Rivastigmine
keywords: Acetylcholinesterase isoform; Chlorpyrifos; Cholinesterase inhibitor; Learning; Memory; Rivastigmine