RT Journal Article
SR Electronic
T1 Higher Binding of the Dopamine D<sub>3</sub> Receptor-Preferring Ligand [<sup>11</sup>C]-(+)-Propyl-Hexahydro-Naphtho-Oxazin in Methamphetamine Polydrug Users: A Positron Emission Tomography Study
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1353
OP 1359
DO 10.1523/JNEUROSCI.4371-11.2012
VO 32
IS 4
A1 Isabelle Boileau
A1 Doris Payer
A1 Sylvain Houle
A1 Arian Behzadi
A1 Pablo M. Rusjan
A1 Junchao Tong
A1 Diana Wilkins
A1 Peter Selby
A1 Tony P. George
A1 Martin Zack
A1 Yoshiaki Furukawa
A1 Tina McCluskey
A1 Alan A. Wilson
A1 Stephen J. Kish
YR 2012
UL http://www.jneurosci.org/content/32/4/1353.abstract
AB Positron emission tomography (PET) findings suggesting lower D2-type dopamine receptors and dopamine concentration in brains of stimulant users have prompted speculation that increasing dopamine signaling might help in drug treatment. However, this strategy needs to consider the possibility, based on animal and postmortem human data, that dopaminergic activity at the related D3 receptor might, in contrast, be elevated and thereby contribute to drug-taking behavior. We tested the hypothesis that D3 receptor binding is above normal in methamphetamine (MA) polydrug users, using PET and the D3-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]-(+)-PHNO). Sixteen control subjects and 16 polydrug users reporting MA as their primary drug of abuse underwent PET scanning after [11C]-(+)-PHNO. Compared with control subjects, drug users had higher [11C]-(+)-PHNO binding in the D3-rich midbrain substantia nigra (SN; +46%; p &lt; 0.02) and in the globus pallidus (+9%; p = 0.06) and ventral pallidum (+11%; p = 0.1), whereas binding was slightly lower in the D2-rich dorsal striatum (approximately −4%, NS; −12% in heavy users, p = 0.01) and related to drug-use severity. The [11C]-(+)-PHNO binding ratio in D3-rich SN versus D2-rich dorsal striatum was 55% higher in MA users (p = 0.004), with heavy but not moderate users having ratios significantly different from controls. [11C]-(+)-PHNO binding in SN was related to self-reported “drug wanting.” We conclude that the dopamine D3 receptor, unlike the D2 receptor, might be upregulated in brains of MA polydrug users, although lower dopamine levels in MA users could have contributed to the finding. Pharmacological studies are needed to establish whether normalization of D3 receptor function could reduce vulnerability to relapse in stimulant abuse.