Brain dopamine transporter messenger RNA and binding sites in cocaine users: a postmortem study.
BACKGROUND
Results of recent radioligand binding experiments suggest that chronic cocaine exposure increases dopamine transporter (DAT) synthesis throughout the striatum of humans. However, detection of cocaine binding site increases in animals and humans has varied depending on the radioligand used. The present experiment tested the hypothesis in cocaine-using humans that synthesis of midbrain DAT messenger RNA increases parallel with increased striatal DAT binding sites.


METHODS
Striatal and midbrain samples were collected during autopsy examination from human cocaine users (n = 34) and from age-, sex-, and race-matched control subjects (n = 36). Levels of DAT messenger RNA were quantified in the medial and lateral midbrain regions using in situ hybridization, and striatal DAT binding sites were assessed by quantitative autoradiography using the DAT-specific radioligand [3H]WIN 35428.


RESULTS
Striatal DAT binding sites were markedly increased in cocaine users, but, paradoxically, medial DAT messenger RNA levels were decreased.


CONCLUSIONS
Cocaine exposure has a marked effect on DAT function, but the mechanisms involved may be complex.
Little
K Y
KY
Department of Psychiatry, University of Michigan, and Ann Arbor Veterans Affairs Medical Center, 48105, USA. kylittle@umich.edu
McLaughlin
D P
DP
Zhang
L
L
McFinton
P R
PR
Dalack
G W
GW
Cook
E H
EH
Cassin
B J
BJ
Watson
S J
SJ
D000328:Adult; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000737:chemistry*; D004298:Dopamine / Q000032:analysis*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493214:SLC6A3 protein, human; C493216:Slc6a3 protein, rat; D004298:Dopamine