Striatal dopaminergic and serotonergic markers in human heroin users.
To establish whether chronic opiate exposure might impair brain dopaminergic or serotonergic function in humans, we assessed biochemical indices of monoaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of the vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. In nucleus accumbens, levels of tyrosine hydroxylase protein (-25%) and those of the dopamine metabolite homovanillic acid (-33%) were reduced significantly together with a trend for decreased dopamine (-32%) concentration. These changes could reflect either a compensatory downregulation of dopamine biosynthesis in response to prolonged dopaminergic stimulation caused by heroin, or reduced axoplasmic transport of tyrosine hydroxylase. Striatal levels of serotonin were either normal or elevated whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were decreased by 27-38%. Our data suggest that chronic heroin exposure might produce a modest reduction in dopaminergic and serotonergic activity that could affect motivational state and impulse control, respectively.
Kish
S J
SJ
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Stephen_Kish@CAMH.net
Kalasinsky
K S
KS
Derkach
P
P
Schmunk
G A
GA
Guttman
M
M
Ang
L
L
Adams
V
V
Furukawa
Y
Y
Haycock
J W
JW
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002352:Carrier Proteins / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006556:Heroin Dependence / Q000378:metabolism* / Q000503:physiopathology; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides; D012701:Serotonin / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015415:Biomarkers; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D004296:Dopa Decarboxylase; D004298:Dopamine; D006719:Homovanillic Acid