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

Animal and human studies suggest a dopamine-mediated effect of styrene neur otoxicity. To date, mechanisms of cerebral membrane transport of neurotrans mitter amines in the presence of styrene in relation to its neurotoxicity h ave not been addressed properly. So, the present study has examined to test the hypothesis that dopaminergic malfunction in vesicular transport is a c ritical component in styrene-induced neurotoxicity in rats. Both styrene an d its intermediate reactive metabolite, styrene oxide antagonized the in vi tro 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 r at 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 pr eloaded into striatal vesicles in vitro. On the other hand, both styrene an d 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 vesicle s, an effect which may be a critical component in styrene-induced neurotoxi city. (C) 1999 Academic Press.