Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder
Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder
复制标题
DOI：
10.1038/s41380-020-00891-4
复制
发表时间：
2020-09-24
影响因子：
11
通讯作者：
Skosnik, Patrick
中科院分区：
文献类型：
--
作者：
D'Souza, Deepak Cyril;Radhakrishnan, Rajiv;Skosnik, Patrick
大麻是最常用和最广泛使用的精神活性药物之一。大麻滥用的比率一直在上升。因此，了解大麻使用对大脑的影响是重要的。反复给药的青少年和成年啮齿动物在突触前和突触后的海马区都显示出持续的微结构变化。在人类吸食大麻的人群中是否存在类似的改变，还没有在体内得到证实。应用正电子发射断层扫描(PET)和突触囊泡糖蛋白2A(SV2A)的放射性配基[C-11]UCB-J，对12例DSM-5大麻使用障碍(CUD)患者和12例匹配的健康对照(HC)进行了体内海马区突触完整性的研究。动脉采血测定血浆输入功能。[11C]以半卵圆中心为参照区，用单组织(1T)隔室模型估计了UCB-J结合势(BPND)。用言语记忆任务评估海马区功能。与HCS相比，CUDS在海马区的[C-11]UCB-JBP(ND)显著降低(接近10%，p=0.008，效应值1.2)，在言语记忆任务中的表现也较差。在校正了体积差异(p=0.013)和年龄和体积校正(p=0.03后)后，这些组在海马体血压(ND)上的差异仍然存在。我们首次在体内证明了大麻使用障碍患者海马区突触密度降低的证据。这些结果与动物大麻素实验研究和人类大脑皮层大体结构研究的显微结构结果一致。较低的海马区突触密度是否与戒断有关，值得进一步研究。
Cannabis is one of the most commonly and widely used psychoactive drugs. The rates of cannabis misuse have been increasing. Therefore, understanding the effects of cannabis use on the brain is important. Adolescent and adult rodents exposed to repeated administration of cannabinoids show persistent microstructural changes in the hippocampus both pre- and post-synaptically. Whether similar alterations exist in human cannabis users, has not yet been demonstrated in vivo. Positron emission tomography (PET) and [C-11]UCB-J, a radioligand for the synaptic vesicle glycoprotein 2A (SV2A), were used to study hippocampal synaptic integrity in vivo in an equal number (n = 12) of subjects with DSM-5 cannabis use disorder (CUD) and matched healthy controls (HC). Arterial sampling was used to measure plasma input function. [11C]UCB-J binding potential (BPND) was estimated using a one-tissue (1T) compartment model with centrum semiovale as the reference region. Hippocampal function was assessed using a verbal memory task. Relative to HCs, CUDs showed significantly lower [C-11]UCB-JBP(ND)in the hippocampus (similar to 10%, p = 0.008, effect size 1.2) and also performed worse on the verbal memory task. These group differences in hippocampalBP(ND)persisted after correction for volume differences (p = 0.013), and correction for both age and volume (p = 0.03). We demonstrate, for the first time, in vivo evidence of lower hippocampal synaptic density in cannabis use disorder. These results are consistent with the microstructural findings from experimental studies with cannabinoids in animals, and studies of hippocampal macrostructure in human with CUD. Whether the lower hippocampal synaptic density resolves with abstinence warrants further study.