title: Dimethoate accelerates the extinction of eyeblink conditioning in mice.
abstract: In agriculture, organophosphates are frequently used as insecticides and pesticides. These compounds decrease acetylcholine esterase (AChE) activity, thereby provoking an accumulation of the neurotransmitter acetylcholine at synapses and resulting in the over-stimulation of acetylcholine receptors. Using trace paradigms, we investigated the effects of dimethoate, a widely used organophosphate insecticide, on the classical conditioning of eyelid responses, a hippocampal-dependent mouse model of associative learning. Mice were conditioned with a trace shock-SHOCK paradigm having first implanted stimulating electrodes in the supraorbitary nerve and recording electrodes in the ipsilateral orbicularis oculi muscle. When these mice were injected with dimethoate (5, 20, 50mg/kg/day) they were capable of acquiring associative learning, and the latency and amplitude of their unconditioned eyelid responses were unaffected by the administration of the pesticide. However, dimethoate administration led to the rapid extinction of conditioned responses, suggesting that this organophosphate accelerates the extinction of this form of associative learning. Analysis of the motor function of these mice using the rotarod performance test revealed that motor function and performance clearly deteriorated following dimethoate administration, with no improvements over the following 4 days. Together these findings indicate that dimethoate accelerates the extinction of acquired conditioned responses, affecting associative learning and memory, and it impairs motor function and performance in mice.
authors.affiliation: Laboratorio de Neurociencia Celular y Plasticidad, Universidad Pablo de Olavide (Edificio 21), Ctra. de Utrera Km 1, 41013 Sevilla, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Valenzuela-Harrington
authors.forename: Irene
authors.initials: I
authors.lastname: Castillo
authors.forename: Corín
authors.initials: C
authors.lastname: Díaz
authors.forename: Inés
authors.initials: I
authors.lastname: Alés
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects*; D003215:Conditioning, Eyelid / Q000187:drug effects*; D004117:Dimethoate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D045442:Rotarod Performance Test
chemical_list: D002800:Cholinesterase Inhibitors; D002802:Cholinesterases; D004117:Dimethoate