期刊
SYNAPSE
卷 64, 期 1, 页码 30-38出版社
WILEY
DOI: 10.1002/syn.20696
关键词
norepinephrine transporter; cocaine abuse; (S,S)-[C-11]O-methylreboxetine; MRB; PET
资金
- National Institute on Drug Abuse [DA019062, R56DA19062, K24DA017899]
- The Patrick and Catherine Weldon Donaghue Medical Research Foundation [DF07-101]
- National Center for Research Resources (NCRR) [UL1 RR024139]
- National Center of PTSD
- Connecticut Department of Mental Health and Addiction Services (DMHAS)
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024139] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K24DA017899, R56DA019062] Funding Source: NIH RePORTER
Objectives: The role of the norepinephrine transporter (NET) in cocaine dependence has never been demonstrated via in vivo imaging due to the lack of suitable NET radioligands. Here we report our preliminary studies evaluting the NET in individuals with cocaine dependence (COC) in comparison to healthy controls (HC) using (S,S)-[C-11]methylreboxetine ([C-11]MRB), the most promising C-11 labeled positron-emission tomography (PET) radioligand for NET developed to date. Methods: Twenty two human volunteers (10 COC and 12 HC) underwent dynamic C-11-MRB-PET acquisition using a High Resolution Research Tomograph (HRRT). Binding potential (BPND) parametric images were computed using the simplified reference tissue model (SRTM2) with occipital cortex as reference region. BPND values were compared between the two groups. Results: Locus coeruleus (LC), hypothalamus, and pulvinar showed a significant inverse correlation with age among HC (age range = 25-54 years; P = 0.04, 0.009, 0.03 respectively). The BPND was significantly increased in thalamus (27%; P < 0.02) and dorsomedial thalamic nuclei (30%; P < 0.03) in COC as compared to HC. Upon age normalization, the upregulation of NET in COC also reached significance in LC (63%, P < 0.01) and pulvinar (55%, P < 0.02) regions. Conclusion: Our results suggest that (a) brain NET concentration declines with age in HC, and (b) there is a significant upregulation of NET in thalamus and dorsomedial thalamic nucleus in COC as compared to HC. Our results also suggest that the use of [C-11]MRB and HRRT provides an effective strategy for studying alterations of the NET system in humans. Synapse 64:30-38, 2010. (C) 2009 Wiley-Liss, Inc.
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