Riga Maurizio S, Soria Guadalupe, Tudela Raúl, Artigas Francesc, Celada Pau
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
Experimental 7T MRI Unit,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona,Spain.
Int J Neuropsychopharmacol. 2014 Aug;17(8):1269-82. doi: 10.1017/S1461145714000261. Epub 2014 Mar 20.
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.
5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）是南美卡皮木饮料中的一种天然致幻剂成分，这种亚马逊地区的饮品传统上用于仪式、宗教和治疗目的，而在美国和欧洲正越来越多地被用于娱乐目的。由于其致幻特性，5-MeO-DMT在精神分裂症研究中具有潜在的研究价值。另外两种拟精神病药物，苯环己哌啶和2,5-二甲氧基-4-碘苯异丙胺（DOI），能显著扰乱啮齿动物内侧前额叶皮质（mPFC）的神经元活动并降低低频皮质振荡（<4Hz，LFCO）的功率。在此，我们研究了5-MeO-DMT对皮质功能的影响以及抗精神病药物对其的潜在逆转作用。此外，通过血氧水平依赖（BOLD）功能磁共振成像（fMRI）评估了脑区活动。5-MeO-DMT扰乱了mPFC的活动，使51%和35%的记录锥体神经元放电增加和减少，并降低了（-31%）LFCO的功率。后一种效应依赖于5-HT1A和5-HT2A受体激活，并被氟哌啶醇、氯氮平、利培酮和mGlu2/3激动剂LY379268逆转。同样，5-MeO-DMT降低了视觉皮质（V1）和mPFC中的BOLD反应。5-MeO-DMT诱导的皮质活动扰乱类似于苯环己哌啶和DOI产生的扰乱。这一点，再加上抗精神病药物的逆转作用，表明观察到的皮质改变与5-MeO-DMT的拟精神病作用有关。总体而言，当前模型可能有助于理解幻觉的神经生物学基础，并在抗精神病药物研发中识别新的靶点。
