title: Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats.
abstract: The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D₂ receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.
authors.affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland.
authors.forename: Mieszko
authors.initials: M
authors.lastname: Olczak
authors.forename: Michalina
authors.initials: M
authors.lastname: Duszczyk
authors.forename: Pawel
authors.initials: P
authors.lastname: Mierzejewski
authors.forename: Ksenia
authors.initials: K
authors.lastname: Meyza
authors.forename: Maria Dorota
authors.initials: MD
authors.lastname: Majewska
mesh_terms: D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012727:Sex Characteristics; D012919:Social Behavior; D013849:Thimerosal / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D017448:Receptors, Dopamine D2; D013849:Thimerosal; D006220:Haloperidol