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 neurotoxicity. However, the results reported to date are incomplete and not consistent. 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 exposure 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-four hours after cessation of such treatment with the higher dose (0.5 g/kg), the contents of dopamine (DA) and its metabolites were significantly reduced in the corpus striatum, hypothalamus, and lateral olfactory tract regions. In vitro styrene showed a significant increase in DA release from rat striatal 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 after cessation of such treatment, along with the recovery of normal levels of dopamine and its metabolites. Furthermore, styrene-induced initial impairments in measures of dopaminergic activity cannot be attributed to altered regulation of tyrosine hydroxylase activity. Specific [3H]-spiroperidol binding was also unaltered 7 or 15 days after subchronic treatment with styrene. These data imply that despite the dopaminergic neuronal loss due to styrene, dopaminergic transmission was not reduced to a level that would result in an overall development of dopamine receptor supersensitivity in the striatum. Collectively, these studies indicate that the subchronic neurotoxic action of styrene may be primarily presynaptic in nature and may involve impaired regulation of DA content and stimulation of DA release.
Chakrabarti
S K
SK
Département de médecine du travail et d'hygiène du milieu, Faculty of Medicine, Université de Montréal, P.O. Box 6128, Main Station, H3C 3J7, Montréal, Québec, Canada.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D020058:Styrene / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D020058:Styrene; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine