Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats

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Persistent behavioral impairments and alterations of brain dopamine

system after early postnatal administration of thimerosal in rats.

<http://www.ncbi.nlm.nih.gov/pubmed/21549155>

Olczak M, Duszczyk M, Mierzejewski P, Meyza K, Majewska MD.

Behav Brain Res. 2011 Apr 28.

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?gHg/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 D(2)

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.