Altered regulation of dopaminergic activity and impairment in motor function in rats after subchronic exposure to styrene

Animal and human studies suggest a dopamine-mediated effect of styrene neur otoxicity. However, the results reported to date are incomplete and not con sistent. As such, the mechanism of its neurotoxicity is still unclear. The present study has, therefore, reexamined the central dopaminergic system in relation to some neurobehavioral effects in rats following subchronic expo sure to styrene. Groups of adult male Sprague-Dawley rats received 0, 0.25, or 0.5 g styrene per kg b.wt. by gavage for 13 consecutive weeks. Twenty-f our hours after cessation of such treatment with the higher dose (0.5 g/kg) , the contents of dopamine (DA) and its metabolites were significantly redu ced in the corpus striatum, hypothalamus, and lateral olfactory tract regio ns. In vitro styrene showed a significant increase in DA release from rat s triatal synaptosomes similar to that of tyramine. Significant loss of motor function was observed on days 56. 70, and 84 during the styrene treatment with the higher dose, and lasted over a month after such treatment. However , the treated animals recovered their motor function within 45-60 days afte r cessation of such treatment, along with the recovery of normal levels of dopamine and its metabolites. Furthermore, styrene-induced initial impairme nts in measures of dopaminergic activity cannot be attributed to altered re gulation of tyrosine hydroxylase activity. Specific [H-3]-spiroperidol bind ing was also unaltered 7 or 15 days after subchronic treatment with styrene . These data imply that despite the dopaminergic neuronal loss due to styre ne, dopaminergic transmission was not reduced to a level that would result in an overall development of dopamine receptor supersensitivity in the stri atum. Collectively, these studies indicate that the subchronic neurotoxic a ction of styrene may be primarily presynaptic in nature and may involve imp aired regulation of DA content and stimulation of DA release. (C) 2000 Else vier Science Inc.