Styrene and styrene oxide affect the transport of dopamine in purified rat striatal synaptic vesicles

Animal and human studies suggest a dopamine-mediated effect of styrene neurotoxicity. To date, mechanisms of cerebral membrane transport of neurotransmitter amines in the presence of styrene in relation to its neurotoxicity have not been addressed properly. So, the present study has examined to test the hypothesis that dopaminergic malfunction in vesicular transport is a critical component in styrene-induced neurotoxicity in rats. Both styrene and its intermediate reactive metabolite, styrene oxide antagonized the in vitro striatal binding of [H-3] tyramine, a putative marker of the vesicular transporter for dopamine. Both styrene and styrene oxide potently inhibited the uptake of [H-3] dopamine in purified synaptic vesicles prepared from rat brain striata, in a dose-related manner, with inhibitory constants (K-i) 2.5 and 2.2 mu M respectively. However, neither styrene nor styrene oxide significantly increased the basal efflux of [H-3] dopamine that has been preloaded into striatal vesicles in vitro. On the other hand, both styrene and styrene oxide have failed to significantly inhibit the uptake of either [H-3] norepinephrine, or [H-3] serotonin into striatal synaptic vesicles. It is concluded that both styrene and styrene oxide are capable of producing impairments in dopaminergic transport in purified striatal synaptic vesicles, an effect which may be a critical component in styrene-induced neurotoxicity. (C) 1999 Academic Press.