title: Dietary nimodipine delays the onset of methylmercury neurotoxicity in mice.
abstract: Adult-onset methylmercury (MeHg) exposure is thought to result primarily in sensory and motor deficits but effects on learning are poorly understood. One mechanism by which chronic MeHg may exert its neurotoxicity is via sustained disruption of intracellular calcium homeostasis, with a consequent increase of intracellular Ca(2+) ions in vulnerable neurons. A biochemically heterogeneous group of compounds, calcium channel blockers, have been shown in vitro to attenuate MeHg's toxicity. To evaluate the role of calcium antagonism in MeHg toxicity in vivo, adult BALB/c mice were exposed chronically to 0 or 15 ppm of Hg (as MeHg) via drinking water and to nimodipine, a dihydropryidine, L-type Ca(2+) channel blocker with action in the CNS. Nimodipine was administered orally in diets (0, 20, or 200 ppm, producing approximately 0, 2, or 20 mg/kg/day of nimodipine). An incremental repeated acquisition (IRA) of response chains procedure was used to detect MeHg-induced deficits in learning or motoric function and to evaluate possible neuroprotection by nimodipine. MeHg impaired performance on the IRA task, and this was partially or completely blocked by dietary nimodipine, depending on dose. Measures of learning co-varied with measures of motoric function as indicated by overall response rate. Nimodipine delayed or prevented the behavioral toxicity of MeHg exposure as evidenced by IRA performance; effects on learning seemed secondary to response rate decreases.
authors.affiliation: Auburn University, Auburn, AL 36849, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Bailey
authors.forename: Blake A
authors.initials: BA
authors.lastname: Hutsell
authors.forename: M Christopher
authors.initials: MC
authors.lastname: Newland
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007858:Learning / Q000187:drug effects; D008297:Male; D020262:Mercury Poisoning, Nervous System / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D008767:Methylmercury Compounds; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D009553:Nimodipine / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D008767:Methylmercury Compounds; D009553:Nimodipine