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

Published:December 02, 2013DOI:https://doi.org/10.1016/j.biopsych.2013.11.022

      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, [11C]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 [11C]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 [11C]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.

      Key Words

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      Linked Article

      • Reductions of p11 and 5-HT1B Receptor Availability in Limbic Brain Regions in Cocaine Dependence
        Biological PsychiatryVol. 76Issue 10
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          Results from the 2012 National Survey on Drug Use and Health reported that approximately 1.6 million individuals aged 12 or over are cocaine abusers in the United States (1). In addition, cocaine abusers often have comorbid disorders, and it has been estimated that 30% to 40% of individuals suffering from drug abuse have a mood or anxiety disorder (2). The high rate of comorbidity between mood disorders and cocaine dependence suggests shared anatomical pathways and molecular mechanisms. Accordingly, it has been reported that both depression and cocaine dependence are associated with alterations in the reward circuitry of the brain, particularly in the nucleus accumbens.
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