Despite the terminology (being “put to sleep” and “waking up”), the effects of anesthesia more closely resemble that of a coma rather than natural sleep—patients are profoundly unresponsive and lack basic reflexes. The drugs used to put a patient to sleep are carefully administered and monitored during a procedure, but waking a patient back up is a much more passive process. Afterwards, the patient simply remains unconscious until their body eliminates the anesthetic used. The time that it takes to achieve wakefulness can vary, which raises the risks of respiratory complications the longer a patient requires artificial ventilation. Upon waking, confusion and grogginess often linger.

The ability to actively wake a patient from general anesthesia could save time in the recovery room, minimize respiratory risks, and possibly help reduce the subsequent mental fog many patients experience. Dopamine—a neurotransmitter associated with wakefulness—is emerging as potential target for the task. A team based in Boston has previously demonstrated that drugs commonly used to treat ADHD, which act upon dopamine in the brain, are capable of arousing rats under continuous steady-state general anesthesia induced by three separate drugs: isoflurane, propofol, and sevoflurane. Now, they are turning their attention to the underlying neural circuitry behind this effect, using optogenetic techniques to specifically test the role of dopamine neurons in waking from anesthesia (Proc. Natl. Acad. Sci. USA 113, 12826–12831; 2016).

The team surgically implanted small optical fibers into the brains of DAT-cre mice, targeting the dopamine receptor-rich ventral tegmental area (VTA). An experimental group of mice was also injected with FLEX-ChR2, a fluorescent channelrhodopsin expressed in dopamine receptors. Dopamine receptors in ChR2+ mice can then be specifically activated using light from the implanted optical fibers.

Upon optical stimulation, all six ChR2+ mice righted themselves, despite continuous administration of isoflurane, while those without the gene remained on their backs. ChR2+ mice whose dopamine receptors were blocked with a D1 agonist also remained unconscious. The righting reflex is an indication of arousal from the coma-like anesthetic state, as rodents will exhibit this response even while sleeping. Further, EEGs of the ChR2+ mice looked similar to those of conscious animals. These results confirm the team's previous hypothesis that dopamine and its associated receptors are actively involved with regaining consciousness from general anesthesia.