Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users.
OBJECTIVE
The hypothesis that human cocaine users lose vesicular monoamine transporter (VMAT2) protein was tested in striatal samples from cocaine users and age-, sex-, and postmortem interval-matched comparison subjects.


METHODS
Striatal samples were retrieved at autopsy; immunoblot assays were then performed by using a highly specific VMAT2 antibody. Striatal radioligand binding to VMAT2 was assessed with dihydrotetrabenazine ([(3)H]DTBZ) and dopamine levels employing high-performance liquid chromatography.


RESULTS
Cocaine users displayed a marked reduction in VMAT2 immunoreactivity as well as reduced [(3)H]DTBZ binding and dopamine levels. It did not appear that the reduction in VMAT2 immunoreactivity was related to ethanol use, but dopamine levels were lower in subjects with only ethanol diagnoses. Subjects suffering from cocaine-induced mood disorders displayed a greater loss of VMAT2 immunoreactivity that approached significance.


CONCLUSIONS
Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely dependent patients.
Little
Karley Y
KY
Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. kylittle@umich.edu
Krolewski
David M
DM
Zhang
Lian
L
Cassin
Bader J
BJ
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009479:Neuropeptides; D012016:Reference Values; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine