title: Dose-response and histopathological study, with special attention to the hypophysis, of the differential effects of domoic acid on rats and mice.
abstract: The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA-inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Lugo, 27002, Spain.
authors.forename: Andrés Crespo
authors.initials: AC
authors.lastname: Vieira
authors.forename: J Manuel Cifuentes
authors.initials: JM
authors.lastname: Martínez
authors.forename: Roberto Bermúdez
authors.initials: RB
authors.lastname: Pose
authors.forename: Álvaro Antelo
authors.initials: ÁA
authors.lastname: Queijo
authors.forename: Nuria Alemañ
authors.initials: NA
authors.lastname: Posadas
authors.forename: Luis M Botana
authors.initials: LM
authors.lastname: López
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008853:Microscopy; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D016019:Survival Analysis
chemical_list: D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid
keywords: domoic acid; hippocampus; histopathology; hypophysis; immunohistochemistry; neurotoxicity