RATIONALE 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. OBJECTIVES We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters' release and rats' behavior in comparison to acute dose. METHODS Changes in dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release were studied using microdialysis in freely moving rats. The hallucinogenic activity was measured in the wet dog shake (WDS) test. The animal locomotion was examined in the open field (OF) test, short-term memory in the novel object recognition (NOR) test. The anxiogenic/anxiolytic properties of the drug were tested using the light/dark box (LDB) test. RESULTS Repeated administration of 25I-NBOMe decreased the response to a challenge dose of DA, 5-HT, and glutamatergic neurons in the frontal cortex as well as weakened the hallucinogenic activity in comparison to acute dose. In contrast, striatal and accumbal DA and 5-HT release and accumbal but not striatal glutamate release in response to the challenge dose of 25I-NBOMe was increased in comparison to acute treatment. The ACh release was increased in all brain regions. Behavioral tests showed a motor activity reduction and memory deficiency in comparison to a single dose and induction of anxiety after the drug's chronic and acute administration. CONCLUSIONS Our findings suggest that multiple injections of 25I-NBOMe induce tolerance to hallucinogenic activity and produce alterations in neurotransmission. 25I-NBOMe effect on short-term memory, locomotor function, and anxiety seems to be the result of complex interactions between neurotransmitter pathways.

中文翻译：

---

对致幻剂 25I-NBOMe 的神经化学和行为影响的耐受性。

基本原理 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethamine (25I-NBOMe) 是一种有效的血清素 5-HT2A/2C 受体激动剂，具有致幻活性。没有关于长期给药后 25I-NBOMe 对脑神经传递和动物性能影响的数据。目的 与急性剂量相比，我们检查了 7 天的 25I-NBOMe（0.3 mg/kg/天）治疗对神经递质释放和大鼠行为的影响。方法 使用微透析在自由活动的大鼠中研究多巴胺 (DA)、血清素 (5-HT)、乙酰胆碱 (ACh) 和谷氨酸释放的变化。致幻活性通过湿狗摇晃（WDS）测试来测量。在旷场（OF）测试中检查动物运动，在新物体识别（NOR）测试中检查短期记忆。使用明/暗盒（LDB）测试来测试药物的致焦虑/抗焦虑特性。结果 与急性剂量相比，重复施用 25I-NBOMe 降低了额叶皮层中 DA、5-HT 和谷氨酸能神经元对攻击剂量的反应，并减弱了致幻活性。相反，与急性治疗相比，响应 25 I-NBOMe 攻击剂量的纹状体和累积区 DA 和 5-HT 释放以及累积区但纹状体谷氨酸释放增加。所有大脑区域的乙酰胆碱释放量均增加。行为测试显示，与单剂量相比，运动活动减少和记忆缺陷，并且在长期和急性给药后会引起焦虑。结论 我们的研究结果表明，多次注射 25I-NBOMe 会诱导对致幻活性的耐受性并产生神经传递的改变。25I-NBOMe 对短期记忆、运动功能和焦虑的影响似乎是神经递质途径之间复杂相互作用的结果。