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. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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