The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study
The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study
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DOI：
10.1007/s00213-014-3523-4
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发表时间：
2014-06-01
影响因子：
3.4
通讯作者：
Howes, Oliver D.
中科院分区：
文献类型：
--
作者：
Bloomfield, Michael A. P.;Morgan, Celia J. A.;Howes, Oliver D.
大麻是世界上使用最广泛的非法药物，经常使用会导致积极性下降，即冷漠。经常长期使用大麻与多巴胺合成能力降低有关。中脑边缘多巴胺能系统通过改变刺激的动机值来调节刺激的加工，而刺激的动机值又由内源性大麻素信号调节。因此，有人提出多巴胺能功能障碍是与慢性大麻使用相关的冷漠的基础。本研究的目的是检查大麻使用者多巴胺能功能和主观冷漠之间的关系。我们通过3,4-二羟基-6-[F-18]-氟-l-苯丙氨酸正电子发射断层扫描测量了14名常规大麻使用者的多巴胺合成能力(以流入速率常数K （i) （cer）为指标），并使用自评冷漠评估量表（AES-S）测量了主观冷漠。所有受试者的AES-S得分均超过34分（中位数[四分位间距]59.5[7.5]），表明根据规范数据存在显著的冷漠。K (i) （cer）与整个纹状体及其关联功能细分的AES-S评分呈负相关（Spearman's rho = -0.64, p = 0.015[整个纹状体]；rho = -0.69, p = 0.006[关联]），但在边缘和感觉运动纹状体细分中无相关。AES-S与当前大麻消费（rho = 0.28, p = 0.34）或首次使用大麻的年龄（rho = 0.25, p = 0.40）之间没有显著关系。这些发现表明，纹状体多巴胺合成能力的降低与慢性大麻使用相关，可能是慢性大麻使用相关的奖励敏感性和动机降低的基础。
Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use.The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users.We measured dopamine synthesis capacity (indexed as the influx rate constant K (i) (cer) ) via 3,4-dihydroxy-6-[F-18]-fluoro-l-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users.All subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K (i) (cer) was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman's rho = -0.64, p = 0.015 [whole striatum]; rho = -0.69, p = 0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho = 0.28, p = 0.34) or age of first cannabis use (rho = 0.25, p = 0.40).These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.