美国加州大学David E. Olson团队的一项最新研究发现了致精神病药物他伯南他洛可不激活邻近即刻早期基因而诱导神经可塑性。2025年8月4日出版的《自然—神经科学》杂志发表了这项成果。

研究团队在啮齿类动物中使用药理学和遗传学工具来证明非致幻性精神塑原通过与经典致幻剂相同的生化途径（包括5-HT2A、TrkB、mTOR和AMPA受体激活）促进皮质神经可塑性，并且TBG诱导的皮质脊髓发生是TBG持续的抗抑郁样行为效果所必需的。与致幻剂相比，TBG不会立即引起谷氨酸爆发或IEG激活。由于这些作用被认为是致幻剂诱导的神经可塑性所必需的，他们的结果揭示了某些精神增塑剂在没有致幻剂作用的情况下促进皮层神经可塑性的机制。

据介绍，非致幻性精神致癌剂，如他伯南他洛（TBG），正在被开发为可能更安全、更可扩展的致幻剂替代品，用于促进神经元生长和治疗各种脑部疾病。目前，尚不清楚5-羟色胺2A （5-HT2A）受体和即时早期基因（IEG）激活是否在非致幻性精神致塑剂的神经可塑性促进作用中起作用。

附：英文原文

Title: The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation

Author: Aarrestad, Isak K., Cameron, Lindsay P., Fenton, Ethan M., Casey, Austen B., Rijsketic, Daniel R., Patel, Seona D., Sambyal, Rohini, Johnson, Shane B., Ly, Calvin, Viswanathan, Jayashri, Barragan, Eden V., Lozano, Stephanie A., Seban, Nicolas, Hu, Hongru, Powell, Noel A., Chytil, Milan, Meyer, Retsina, Rose, David, Hempel, Chris, Olson, Eric, Hansen, Hanne D., Madsen, Clara A., Knudsen, Gitte M., Redd, Chase, Wheeler, Damian G., Guanzon, Nathaniel, Muir, Jessie, Hennessey, Joseph J., Quon, Gerald, McCorvy, John D., Gandhi, Sunil P., Rasmussen, Kurt, Liston, Conor, Gray, John A., Heifets, Boris D., Nord, Alex S., Kim, Christina K., Olson, David E.

Issue&Volume: 2025-08-04

Abstract: Nonhallucinogenic psychoplastogens, such as tabernanthalog (TBG), are being developed as potentially safer, more scalable alternatives to psychedelics for promoting neuronal growth and treating various brain conditions. Currently, it is unclear whether 5-hydroxytryptamine 2A (5-HT2A) receptors and immediate early gene (IEG) activation have a role in the neuroplasticity-promoting effects of nonhallucinogenic psychoplastogens. Here, we use pharmacological and genetic tools in rodents to show that nonhallucinogenic psychoplastogens promote cortical neuroplasticity through the same biochemical pathway—involving 5-HT2A, TrkB, mTOR and AMPA receptor activation—as classic psychedelics and that TBG-induced cortical spinogenesis is required for the sustained antidepressant-like behavioral effect of TBG. In contrast to psychedelics, TBG does not induce an immediate glutamate burst or IEG activation. As these effects have been assumed to be necessary for psychedelic-induced neuroplasticity, our results shed light on the mechanisms by which certain psychoplastogens can promote cortical neuroplasticity in the absence of hallucinogenic effects.

DOI: 10.1038/s41593-025-02021-1

Source: https://www.nature.com/articles/s41593-025-02021-1