内源性大麻素对健康志愿者中枢血清素活性的调节。

IF 3.6 3区 医学 Q1 PSYCHIATRY
Barbara Emons, Larissa Arning, Vera-Estelle Makulla, Maria-Theresia Suchy, Dimitrios Tsikas, Thomas Lücke, Jörg T Epplen, Georg Juckel, Patrik Roser
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引用次数: 0

摘要

背景:血清素能和内源性大麻素系统参与抑郁症的病因学。抑郁症患者表现为血清素能活性低,内源性大麻素anandamide (AEA)和2-花生四烯酰基甘油(2AG)水平下降。由于大麻素(CB) 1受体被内源性配体如AEA和2AG激活,其浓度分别由脂肪酸酰胺水解酶(FAAH)和单酰基甘油脂肪酶控制,因此我们研究了对血清素能利用的影响。在这项研究中,我们研究了编码内源性大麻素CB1受体的大麻素受体1 (CNR1)基因rs1049353单核苷酸多态性(SNP)和FAAH基因rs324420 SNP对59名健康志愿者血清素能和内源性大麻素系统的影响。方法:采用听觉诱发电位(LDAEP)响度依赖性法测定血清素能活性。用质谱法测定AEA、2AG及其非活性异构体1AG的血浆浓度。采用聚合酶链反应(PCR)和PCR限制性片段长度多态性差异酶分析法对两个snp (rs1049353、rs344420)进行基因分型。结果:5 -羟色胺能活性和内源性大麻素浓度的基因型分布无明显差异。然而,在详细考虑了cnr1 -a等位基因载体后,降低了AEA (a等位基因载体M = 0.66, SD = 0.24;GG基因型M = 0.72, SD = 0.24)和2AG (a等位基因携带者M = 0.70, SD = 0.33;GG基因型M = 1.03, SD = 0.83)血药浓度,血清素能活性与AEA和2AG浓度之间存在相关性。结论:我们的研究结果表明,携带CNR1-A等位基因的人可能更容易患抑郁症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers.

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers.

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers.

Background: The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.

Methods: Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.

Results: Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.

Conclusions: Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.

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来源期刊
CiteScore
6.60
自引率
2.70%
发文量
43
审稿时长
>12 weeks
期刊介绍: Annals of General Psychiatry considers manuscripts on all aspects of psychiatry, including neuroscience and psychological medicine. Both basic and clinical neuroscience contributions are encouraged. Annals of General Psychiatry emphasizes a biopsychosocial approach to illness and health and strongly supports and follows the principles of evidence-based medicine. As an open access journal, Annals of General Psychiatry facilitates the worldwide distribution of high quality psychiatry and mental health research. The journal considers submissions on a wide range of topics including, but not limited to, psychopharmacology, forensic psychiatry, psychotic disorders, psychiatric genetics, and mood and anxiety disorders.
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