Modulating anesthetic emergence with pathway-selective dopamine signaling

Purpose of review To summarize the recent preclinical findings investigating dopaminergic circuits for their involvement in reversing anesthetic-induced unconsciousness. Recent findings 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. Summary 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.