Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans

Background Preclinical evidence implicates the serotonin receptor 5-hydroxytryptamine 1B (5-HT1B ) in the effects of cocaine. This study explores 5-HT1B in humans by examining receptor availability in vivo in subjects whose primary addiction is cocaine dependence (CD) using positron emission tomogra...

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Published in:	Biological psychiatry (1969) 2014-11, Vol.76 (10), p.816-822
Main Authors:	Matuskey, David, Bhagwagar, Zubin, Planeta, Beata, Pittman, Brian, Gallezot, Jean-Dominique, Chen, Jason, Wanyiri, Jane, Najafzadeh, Soheila, Ropchan, Jim, Geha, Paul, Huang, Yiyun, Potenza, Marc N, Neumeister, Alexander, Carson, Richard E, Malison, Robert T
Format:	Article
Language:	eng
Subjects:	5-HT1B Addictive behaviors Adult Adult and adolescent clinical studies Biological and medical sciences Brain - diagnostic imaging Brain - metabolism Carbon Radioisotopes cocaine Cocaine-Related Disorders - diagnostic imaging Cocaine-Related Disorders - metabolism Drug addiction Female human Humans Magnetic Resonance Imaging Male Medical sciences PET Positron-Emission Tomography Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptor, Serotonin, 5-HT1B - metabolism serotonin VBM
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Summary:	Background Preclinical evidence implicates the serotonin receptor 5-hydroxytryptamine 1B (5-HT1B ) in the effects of cocaine. This study explores 5-HT1B in humans by examining receptor availability in vivo in subjects whose primary addiction is cocaine dependence (CD) using positron emission tomography. Methods Study participants included 14 medically healthy subjects with CD (mean age = 41 ± 6 years) who were compared with 14 age-matched healthy control subjects (mean age = 41 ± 8 years) with no past or current history of cocaine or other illicit substance abuse. Participants underwent magnetic resonance imaging followed by positron emission tomography with the highly selective 5-HT1B tracer, [11 C]P943, for purposes of quantifying regional binding potential. Voxel-based morphometry and gray matter masking also were employed to control for potential partial volume effects. Results The [11 C]P943 positron emission tomography imaging data in nine candidate regions (amygdala, anterior cingulate cortex, caudate, frontal cortex, hypothalamus, pallidum, putamen, thalamus, and ventral striatum) showed significant or nearly significant reductions of regional binding potential in subjects with CD in three regions: anterior cingulate (−16%, p < .01), hypothalamus (−16%, p = .03), and frontal cortex (−7%, p = .08). Voxel-based morphometry showed significant gray matter reductions in the frontal cortex of subjects with CD. After gray matter masking, statistically significant reductions in the [11 C]P943 regional binding potential were either retained (anterior cingulate, −14%, p = .01; hypothalamus, −20%, p < .01) or achieved (frontal cortex, −14%, p < .01). Whole-brain voxel-wise parameter estimation confirmed these results. Secondary analyses were also significant in some regions for years of cocaine and daily tobacco use. Conclusions The reductions found in this study suggest that 5-HT1B receptors may contribute to the etiology or expression of CD and potentially represent a target for medication development.
ISSN:	0006-3223 1873-2402