A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons
A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons
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DOI：
10.2131/jts.41.813
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发表时间：
2016-12-01
影响因子：
2
通讯作者：
Kaneko, Shuji
中科院分区：
文献类型：
--
作者：
Asaoka, Nozomi;Kawai, Hiroyuki;Kaneko, Shuji
N-[[1-（5-氟戊基）- 1h -茚唑-3基]羰基]-3-甲基- d -缬氨酸甲酯（5F-ADB）是一种最有效的合成大麻素，可引起人类严重的精神病症状，有时可导致死亡。为了研究其毒性背后的神经元机制，我们研究了5F-ADB对中脑多巴胺能和血清素能系统的影响，这些系统调节各种基本的大脑功能，如奖励相关行为。体外电生理技术记录5f - adb诱导的多巴胺能和血清素能神经元自发放电活性的变化。在多巴胺能神经元中，5F-ADB （1 μ M）显著提高了自发放电率，而5F-ADB在CBl拮抗剂AM251 （1 μ M）存在下不能激活多巴胺能神经元。然而，相同浓度的5F-ADB不影响血清素能神经元的活性。这些结果表明5F-ADB激活局部CB受体，增强中脑多巴胺能系统，但对中脑血清素能系统没有直接影响。
N-[[1-(5-fluoropentyl)-1H-indazol-3 yl] carbonyl]-3-methyl-D-valine methyl ester (5F-ADB) is one of the most potent synthetic cannabinoids and elicits severe psychotic symptoms in humans, sometimes causing death. To investigate the neuronal mechanisms underlying its toxicity, we examined the effects of 5F-ADB on midbrain dopaminergic and serotonergic systems, which modulate various basic brain functions such as those in reward-related behavior. 5F-ADB-induced changes in spontaneous firing activity of dopaminergic and serotonergic neurons were recorded by ex vivo electrophysiological techniques. In dopaminergic neurons, 5F-ADB (1 mu M) significantly increased the spontaneous firing rate, while 5F-ADB failed to activate dopaminergic neurons in the presence of the CBl, antagonist AM251 (1 mu M). However, the same concentration of 5F-ADB did not affect serotonergic-neuron activity. These results suggest that 5F-ADB activates local CB, receptors and potentiates midbrain dopaminergic systems with no direct effects on midbrain serotonergic systems.