Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital.
Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Anaesthesiol. 2023 Oct 1;36(5):468-475. doi: 10.1097/ACO.0000000000001293. Epub 2023 Jul 10.
To summarize the recent preclinical findings investigating dopaminergic circuits for their involvement in reversing anesthetic-induced unconsciousness.
The release of dopamine from the ventral tegmental area onto dopamine D1 receptor-expressing neurons in the nucleus accumbens promotes emergence following general anesthesia. Two relevant targets of dopamine D1 receptor-expressing neurons in the nucleus accumbens include the lateral hypothalamus and ventral pallidum. Activating mesocortical dopaminergic projections from the ventral tegmental area to the prelimbic cortex has also been shown to hasten emergence from general anesthesia. In contrast, the nigrostriatal dopamine pathway is not involved in regulating anesthetic emergence. The role of the tuberoinfundibular endocrine dopamine pathway remains to be tested; however, recent studies have identified an important function of neuroendocrine signaling on modulating general anesthesia.
Potential avenues for accelerating anesthetic emergence may be found through targeting specific arousal-promoting pathways in the brain. Accumulating evidence from rodent studies manipulating cell type- and circuit-specific signaling pathways have identified dopamine as a potent modulator of general anesthesia. Specifically, dopamine signaling along the mesolimbic and mesocortical pathways plays a fundamental role in regulating consciousness.
总结近期关于多巴胺能回路在逆转麻醉诱导意识丧失中的作用的临床前研究结果。
腹侧被盖区多巴胺释放到伏隔核中多巴胺 D1 受体表达神经元,促进全身麻醉后的苏醒。伏隔核中多巴胺 D1 受体表达神经元的两个相关靶点包括外侧下丘脑和腹侧苍白球。激活腹侧被盖区到前额叶皮层的中脑皮质多巴胺投射也被证明可以加速全身麻醉的苏醒。相比之下,黑质纹状体多巴胺通路不参与调节麻醉苏醒。调节神经内分泌信号的神经内分泌多巴胺通路的作用仍有待检验;然而,最近的研究已经确定了神经内分泌信号在调节全身麻醉中的重要作用。
通过靶向大脑中特定的觉醒促进途径,可能会找到加速麻醉苏醒的方法。操纵细胞类型和回路特异性信号通路的啮齿动物研究的累积证据表明,多巴胺是全身麻醉的一种有效调节剂。具体而言,中脑边缘和中皮质通路的多巴胺信号在调节意识方面起着至关重要的作用。