title: Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.
abstract: Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system.
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil. Electronic address: godinho@ibb.unesp.br.
authors.forename: Antonio Francisco
authors.initials: AF
authors.lastname: Godinho
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Oliveira Souza
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Caio Cristóvão
authors.initials: CC
authors.lastname: Carvalho
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Daniel França
authors.initials: DF
authors.lastname: Horta
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Daniel
authors.initials: D
authors.lastname: De Fraia
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Anselmo
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: João Leandro
authors.initials: JL
authors.lastname: Chaguri
authors.affiliation: Center of Toxicological Assistance (CEATOX), Biosciences Institute, Paulista State University (UNESP), Campus of Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, s/n, CEP 18618-689, Botucatu, SP., Brasil.
authors.forename: Caique Aparecido
authors.initials: CA
authors.lastname: Faria
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010575:Pesticides / Q000633:toxicity*; D010852:Picrotoxin / Q000494:pharmacology; D010865:Pilot Projects; D011720:Pyrazoles / Q000633:toxicity*; D011897:Random Allocation; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D018756:GABA Antagonists; D010575:Pesticides; D010852:Picrotoxin; D011720:Pyrazoles; D011963:Receptors, GABA-A; C082360:fipronil
keywords: GABA; fipronil; memory behavior; pesticide; picrotoxin