title: Effects of subchronic exposure to styrene on the extracellular and tissue levels of dopamine, serotonin and their metabolites in rat brain.
abstract: At present, there is controversy over the neurotoxic potential of styrene. Several epidemiological and clinical studies have shown that styrene exposure causes alterations of central nervous system functions in humans. Neurotransmitters have been implicated in the pathogenesis of styrene neurotoxicity in rodents. Several studies carried out on postmortem brain tissue suggest that styrene may alter dopaminergic neurotransmission in rabbit or rat brain. Moreover, in vitro studies suggest that both styrene and styrene oxide inhibit the uptake of dopamine (DA) in purified synaptic vesicles prepared from rat brain striata. To date, biochemical studies on animals have explored global tissue levels of neurotransmitters with sub-acute exposures to styrene. However, extracellular levels of neurotransmitters are more closely related to behaviour than are global tissue levels. The present study determined changes in the extracellular concentrations of DA, serotonin (5-HT) and their acid metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA), in striatal dialysates from freely moving adult male rats after exposure to 750 and 1,000 ppm styrene, 6 h per day, 5 days per week for 4 weeks. We also determined the concentrations of DA, 5-HT and their acid metabolites in striatum, nucleus accumbens and prefrontal cortex obtained postmortem from similarly exposed rats. Exposure to 1,000 ppm of styrene caused a significant decrease in extracellular acid metabolite concentrations. Tissue levels of acid metabolites were also decreased to a lesser extent. The effects were observed 72 h after discontinuing exposure but had vanished 17 days later. There was no change in DA or 5-HT concentrations either in the dialysates or tissues. Exposure to 750 ppm styrene caused no changes in the concentrations of DA, 5-HT and their acid metabolites either in the dialysates or tissues. The possibility that the effect of styrene is mediated by monoamine oxidase (MAO) inhibition is discussed.
authors.affiliation: Département Polluants et Santé, Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP 27, 54501, Vandoeuvre cedex, France. francois.gagnaire@inrs.fr
authors.forename: F
authors.initials: F
authors.lastname: Gagnaire
authors.forename: M
authors.initials: M
authors.lastname: Chalansonnet
authors.forename: N
authors.initials: N
authors.lastname: Carabin
authors.forename: J-C
authors.initials: JC
authors.lastname: Micillino
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D017551:Microdialysis; D009068:Movement / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D020058:Styrene / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D020058:Styrene; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid