Serotonin 1B receptor imaging in alcohol dependence.
BACKGROUND
Although animal models suggest that alcohol dependence (AD) is associated with elevations in the number of serotonin 1B receptors (5-HT(1B)R), 5-HT(1B)R levels have not been investigated in people with AD. The selective 5-HT(1B)R antagonist radioligand, [(11)C]P943, permits in vivo assessment of central 5-HT(1B)R binding potential (BP(ND)) with positron emission tomography. Because of its central role in AD, we were particularly interested in ventral striatal 5-HT(1B)R BP(ND) values.


METHODS
Twelve medication-free, recently abstinent (at least 4 weeks) patients with AD (mean age 35.2 +/- 10.2 years, 5 women) and 12 healthy control subjects (HC) (mean age 30.6 +/- 9.2 years, 5 women) completed [(11)C]P943 positron emission tomography on a high-resolution research tomograph. Individual magnetic resonance imaging scans were collected to exclude individuals with anatomical abnormalities and for coregistration. Imaging data were analyzed with a multilinear reference tissue model.


RESULTS
Ventral striatal 5-HT(1B)R BP(ND) values (2.01 +/- .57% and 1.55 +/- .09%, respectively; 29% between-group difference, p = .006) were increased in AD compared with HC subjects. No influence of demographic or clinical variables or amount of injected radiotracer was observed.


CONCLUSIONS
This study provides the first evidence that AD in humans is, like in rodent models, associated with increased levels of ventral striatal 5-HT(1B)Rs.
Hu
Jian
J
Molecular Imaging Program, Clinical Neurosciences Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Henry
Shannan
S
Gallezot
Jean-Dominique
JD
Ropchan
Jim
J
Neumaier
John F
JF
Potenza
Marc N
MN
Sinha
Rajita
R
Krystal
John H
JH
Huang
Yiyun
Y
Ding
Yu-Shin
YS
Carson
Richard E
RE
Neumeister
Alexander
A
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011760:Pyrrolidinones / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism*; D018709:Statistics, Nonparametric; D055815:Young Adult
C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D010879:Piperazines; D011760:Pyrrolidinones; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists