Dopamine is a catecholaminergic neurotransmitter found in central and peripheral tissues and is involved in a variety of physiological and neurological processes.1 Neurons that synthesize and release dopamine form dopaminergic pathways, which play an important role in physiological arousal.2,3 Recent studies propose that dopaminergic pathways in the brain may be activated to promote emergence from general anesthesia.4
In current clinical practice, emergence from general anesthesia is treated as a passive process focused on anesthetic drug elimination.4 Difficulty with emergence is a common cause of airway or oxygenation problems, which contribute to morbidity in surgical patients.4 Clinical problems related to emergence from general anesthesia is estimated to occur in approximately 5% of adults and up to 30% of children.4 Evidence from three recent studies suggest a potential functional role of dopaminergic pathways in the decreasing the time for emergence from general anesthesia.2
Accumulating evidence suggests that the process of inducing general anesthesia is distinct from the process of emergence, leading to a growing interest in the role of ascending arousal pathways in emergence.3 A 2013 study sponsored by the American Society of Anesthesiologists tested the hypothesis that activation of dopaminergic receptors decreases emergence time and induces recovery from general anesthesia.2,3 The results showed that the dopaminergic receptor agonist chloro-APB decreased time to emergence, whereas when the dopaminergic receptor antagonist SCH-23390 was administered, the chloro-APB-induced arousal response was inhibited.3 These results strongly suggest that the arousal response is specifically mediated by the dopaminergic pathway.3
In 2014, researchers conducted a study to test whether electrical stimulation of dopaminergic nuclei also causes emergence from general anesthesia.4 In mammals, the two major dopamine nuclei, the ventral tegmental area (VTA) and the substantia nigra (SN), are located in the midbrain.4 In the experiment, a bipolar stainless-steel electrode was placed in either the VTA or the SN in adult rats.4 The results showed that electrical stimulation of the VTA, but not of the SN, evoked arousal from anesthesia with isoflurane or propofol.4 These results suggest that dopamine released by VTA neurons, but not SN neurons, induce emergence from general anesthesia.4
The results from a 2016 study conducted by researchers at Massachusetts General Hospital similarly found that selective activation of VTA neurons induced a profound behavioral arousal response in anesthetized mice.5 A notable finding from the study was that VTA neurons have comparable mean firing rates over sleep-wake cycles, suggesting that they are not involved in sleep-wake transitions.5 However, general anesthesia produces a state of unresponsiveness that is distinct from natural sleep.5 Therefore, the results from the study support the idea that the neural mechanisms underlying emergence from general anesthesia are different than those governing awakening from natural sleep.5 Although VTA neurons may not play a significant role in regulating sleep-wake transitions, they may be critically involved in initiating emergence from general anesthesia.5
In summary, the neural mechanisms underlying emergence from general anesthesia are not well understood.2,5 However, a growing body of literature indicates that dopaminergic pathways are involved with emergence from general anesthesia.2 The activation of neurons in the VTA of mice has been associated with faster emergence from anesthesia, which may provide a novel approach to improving recovery from general anesthesia in surgical patients.2,4,5
References
- Vidal, P. M., & Pacheco, R. (2019). Targeting the dopaminergic system in autoimmunity. Journal of Neuroimmune Pharmacology, 1-17. doi:10.1007/s11481-019-09834-5
- Zhou, X., Wang, Y., Zhang, C., et al. (2015). The Role of Dopaminergic VTA Neurons in General Anesthesia. PLOS ONE, 10(9). doi:10.1371/journal.pone.0138187
- Taylor, N. E., Chemali, J. J., Brown, E. N., & Solt, K. (2013). Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology, 118(1), 30-39. doi:10.1097/ALN.0b013e318278c896
- Solt, K., Van Dort, C. J., Chemali, J. J., et al. (2014). Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology, 121(2), 311-319. doi:10.1097/ALN.0000000000000117
- Taylor, N. E., Van Dort, C. J., Kenny, J. D., et al. (2016). Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. Proceedings of the National Academy of Sciences, 113(45), 12826-12831. doi:10.1073/pnas.1614340113
