title: Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.
abstract: Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended.
authors.affiliation: Departamento de Psicología y Sociología, Facultad de Ciencias Sociales y Humanas, Universidad de Zaragoza, Campus Ciudad Escolar, 44003 Teruel, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: López-Granero
authors.affiliation: Departamento de Psicología, Universidad de Almería, Campus de Excelencia Internacional Agroalimentario CeiA3, La Cañada, 04120 Almería, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ruiz-Muñoz
authors.affiliation: Departamento de Psicología, Universidad de Almería, Campus de Excelencia Internacional Agroalimentario CeiA3, La Cañada, 04120 Almería, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Nieto-Escámez
authors.affiliation: Research in Neurobehavior and Health (NEUROLAB), and Research Center in Behavioral Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: María T
authors.initials: MT
authors.lastname: Colomina
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, Bronx, 10461 NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Departamento de Psicología, Universidad de Almería, Campus de Excelencia Internacional Agroalimentario CeiA3, La Cañada, 04120 Almería, Spain. Electronic address: fsanchez@ual.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sánchez-Santed
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003463:Cues; D003975:Diazepam / Q000627:therapeutic use; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy; D057567:Memory, Long-Term / Q000187:drug effects; D009068:Movement / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010775:Photic Stimulation; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate; D004390:Chlorpyrifos; D003975:Diazepam
keywords: Chlorpyrifos dietary; Chronic; GABAergic system; Glutamatergic system; Long-term spatial memory; Thigmotaxis