中国药科大学药学院龙燕等合作的一项最新研究,提出了一个前边缘皮层-下丘脑外侧回路调节阿普唑仑诱导的雄性小鼠条件位置偏好的获得。该研究于2026年8月19日发表于《中国药理学报》杂志上。
研究人员第一次建立Alp管理是在10点mg/kg可靠诱导雄性小鼠条件位置偏好(CPP)。结果表明,alp训练小鼠的前边缘皮质(PrL)CaMKⅡα神经元过度活跃。PrL CaMKⅡα神经元活性的化学发生调控双向获得alp诱导的CPP。
此外,virthem示踪显示PrL CaMKⅡα神经元向外侧下丘脑(LH)强烈投射。抑制PrL-LH回路可显著降低alp诱导的CPP的获得,而增强该回路可促进alp诱导的CPP。激活PrLCaMKⅡα-LH电路不能产生实时位置偏好。综上所述,他们的研究结果表明,PrL谷氨酸能神经元和PrL- lh回路调节了Alp诱导的奖励记忆形成,为阐明Alp成瘾的神经机制提供了基础。
研究人员表示,阿普唑仑(Alprazolam,简称Alp)是一种高效苯二氮卓类药物,具有显著的精神失常和成瘾风险,但与Alp相关的奖励记忆的确切机制尚不明确。
附:英文原文
Title: A prelimbic cortex-lateral hypothalamus circuit regulates acquisition of alprazolam-induced conditioned place preference in male mice
Author: Song, Zhi-peng, Li, Nian-ci, Song, Rui, Zheng, Cheng, Wang, Cun, Liao, Fei-zhi, Tang, Su-su, Yuan, Dan-hua, Hong, Hao, Chen, Zhi-gang, Long, Yan
Issue&Volume: 2026-08-19
Abstract: Alprazolam (Alp), a high-potency benzodiazepine, poses a significant risk of abuse and addiction, yet the precise mechanisms underlying Alp-associated reward memory remain poorly defined. Here, we first established that administration of Alp at 10mg/kg reliably induces conditioned place preference (CPP) in male mice. Our results indicated that prelimbic cortex (PrL) CaMKⅡα neurons were hyperactive in Alp-trained mice. Chemogenetic manipulation of the activity of PrL CaMKⅡα neurons bidirectionally regulated acquisition of Alp-induced CPP. Furthermore, virus tracing indicated a strong PrL CaMKⅡα neuron projection to lateral hypothalamus (LH). Suppression of the PrL-LH circuit significantly decreased acquisition of Alp-induced CPP, while potentiation of this circuit facilitated Alp-induced CPP. Activation of PrLCaMKⅡα-LH circuit failed to produce real-time place preference. In summary, our results indicate that PrL glutamatergic neurons and the PrL-LH circuit regulate Alp-induced reward memory formation, providing a foundation for elucidating the neural mechanisms underlying Alp addiction.
DOI: 10.1038/s41401-026-01909-3
Source: https://www.nature.com/articles/s41401-026-01909-3
Acta Pharmacologica Sinica:《中国药理学报》,创刊于1980年。隶属于施普林格·自然出版集团,最新IF:8.2
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