Striatal dopaminergic and serotonergic markers in human heroin users

To establish whether chronic opiate exposure might impair brain dopaminergi c or serotonergic function in humans, we assessed biochemical indicts of mo noaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of t he vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. III nucleus ac cunbens, levels of tyrosine hydroxylase protein (-25%) and those of the dop amine metabolite homovanillic acid (-33%) were reduced significantly togeth er with a trend for decreased dopamine (-32%) concentration. These changes could reflect tither a compensatory downregulation of dopamine biosynthesis in response to prolonged dopaminergic stimulation caused by heroin, or red uced axoplasmic transport of tyrosine hydroxylase. Striatal levels of serot onin were either normal or elevated whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were decreased by 27-38%. Our data s uggest that chronic heroin exposure might produce a modest reduction in dop aminergic and serotonergic activity that could affect motivational state an d impulse control, respectively. (C) 2001 American College of Neuropsychoph armacology. Published by Elsevier Science Inc.