Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users.
Animal data have long suggested that an adaptive upregulation of nucleus accumbens dopamine D1 receptor function might underlie part of the dependency on drugs of abuse. We measured by quantitative immunoblotting protein levels of dopamine D1 and, for comparison, D2 receptors in brain of chronic users of methamphetamine, cocaine, and heroin. As compared with the controls, brain dopamine D1 receptor concentrations were selectively increased (by 44%) in the nucleus accumbens of the methamphetamine users, whereas a trend was observed in this brain area for reduced protein levels of the dopamine D2 receptor in all three drug groups (-25 to -37%; P < 0.05 for heroin group only). Our data support the hypothesis that aspects of the drug-dependent state in human methamphetamine users might be related to increased dopamine D1 receptor function in limbic brain.
Worsley
J N
JN
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Moszczynska
A
A
Falardeau
P
P
Kalasinsky
K S
KS
Schmunk
G
G
Guttman
M
M
Furukawa
Y
Y
Ang
L
L
Adams
V
V
Reiber
G
G
Anthony
R A
RA
Wickham
D
D
Kish
S J
SJ
D000328:Adult; D000368:Aged; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D002908:Chronic Disease; D003001:Cloning, Molecular; D019970:Cocaine-Related Disorders / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects*; D006556:Heroin Dependence / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D008694:Methamphetamine