title: Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation, and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats exposed to the organophosphate chlorpyrifos.
abstract: Intermittent or continuous exposure to a wide variety of chemically unrelated environmental pollutants might result in the development of multiple chemical intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical evidence suggests that exposure to organophosphates might be linked to increased ethanol sensitivity and reduced voluntary consumption of ethanol-containing beverages in humans. The growing body of clinical and experimental evidence emerging in this new scientific field that bridges environmental health sciences, toxicology, and drug research calls for well-controlled studies aimed to analyze the nature of the neurobiological interactions of drugs and pollutants. Present study specifically evaluated neurobiological and behavioral responses to ethanol in Wistar rats that were previously exposed to the pesticide organophosphate chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a single injection of CPF showed long-lasting ethanol avoidance that was not secondary to altered gustatory processing or enhancement of the aversive properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced sedation without altering blood ethanol levels. An immunocytochemical assay revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF treatment, a critical brain area that has been implicated in ethanol intake and sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral acetylcholinesterase inhibition) in neuronal pathways critically involved in neurobiological responses to ethanol.
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, University of Almería, 04120 Almería, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.forename: Matilde
authors.initials: M
authors.lastname: López-Grancha
authors.forename: Montserrat
authors.initials: M
authors.lastname: Navarro
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Sánchez-Amate
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cubero
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002755:Choice Behavior / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D002802:Cholinesterases / Q000378:metabolism; D016292:Procedural Sedation; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005726:Ganglia, Parasympathetic / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007279:Injections, Subcutaneous; D008297:Male; D010755:Organophosphates / Q000008:administration & dosage / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol; D002802:Cholinesterases; D004390:Chlorpyrifos