Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction.
BACKGROUND
Positron emission tomography (PET) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3) receptor binding and decreased presynaptic dopamine release in the striatum. Some studies have also shown that these reductions are associated with the severity of addiction. For example, in cocaine dependence, low dopamine release is associated with the choice to self-administer cocaine. The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior.


METHODS
Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration (methylphenidate) to measure striatal D(2/3) receptor binding and presynaptic dopamine release. After the PET scans, the heroin-dependent subjects performed heroin self-administration sessions.


RESULTS
Both striatal D(2/3) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects. However, neither PET measure of dopamine transmission predicted the choice to self-administer heroin.


CONCLUSIONS
These findings show that heroin addiction, like addiction to other drugs of abuse, is associated with low D(2/3) receptor binding and low presynaptic dopamine. However, neither of these outcome measures was associated with the choice to self-administer heroin.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. dm437@columbia.edu
Diana
D
Martinez
Phillip A
PA
Saccone
Fei
F
Liu
Mark
M
Slifstein
Daria
D
Orlowska
Alex
A
Grassetti
Stephanie
S
Cook
Allegra
A
Broft
Ronald
R
Van Heertum
Sandra D
SD
Comer
D000328:Adult; D016739:Behavior, Addictive / Q000378:metabolism* / Q000523:psychology*; D002755:Choice Behavior; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology; D006556:Heroin Dependence / Q000378:metabolism* / Q000523:psychology; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D059906:Neuroimaging / Q000379:methods / Q000523:psychology; D049268:Positron-Emission Tomography / Q000379:methods / Q000523:psychology; D017729:Presynaptic Terminals / Q000378:metabolism; D020891:Raclopride; D011869:Radioligand Assay / Q000379:methods / Q000523:psychology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012646:Self Administration / Q000379:methods / Q000523:psychology
D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D020891:Raclopride; D003932:Heroin; D004298:Dopamine