Nucleus Accumbens Dopamine Levels Fluctuate Across Different States of Consciousness Under Sevoflurane Anesthesia

Dopamine (DA) is a critical neurotransmitter that regulates many physiological and behavioral processes. The central dopaminergic system plays a pivotal role in modulating general anesthesia (GA). DA release in the brain is mainly concentrated in the nucleus accumbens (NAc), prefrontal cortex, hypothalamus, and dorsal striatum. Several NAc neuron subtypes are essential for modulating states of consciousness during GA. However, whether NAc DA signal dynamics correlate with different states of consciousness under sevoflurane anesthesia remains to be elucidated. In this study, we measured the dynamic fluctuations of NAc DA levels throughout sevoflurane anesthesia to verify its role.

An intensity-based genetically encoded DA indicator, dLight1.1, was employed to track DA release in the NAc. Fiber photometry combined with electroencephalogram/electromyogram recordings was employed to synchronously track NAc DA signal dynamics across different states of consciousness under sevoflurane anesthesia.

Under 2.5% sevoflurane exposure, DA release in the NAc significantly increased during the initial 100 s of sevoflurane induction, which was designated as sevo on-1 (mean ± standard error of the mean [SEM]; baseline vs. sevo on-1, p = 0.0261), and continued to decrease in the subsequent anesthesia maintenance phases (sevo on-1 vs. sevo on-4, p = 0.0070). Following the cessation of sevoflurane administration (with intervals denoted as sevooff), NAc DA gradually returned to baseline levels (sevo on-1 vs. sevo off-1, p = 0.0096; sevo on-1 vs. sevo off-3, p = 0.0490; sevo on-1 vs. sevo off-4, p = 0.0059; sevo on-4 vs. sevo off-4, p = 0.0340; sevo off-1 vs. sevo off-4, p = 0.0451). During the induction phase, NAc DA signal dynamics markedly increased during the pre-loss of consciousness (LOC) period (pre-anesthesia baseline vs. pre-LOC, p = 0.0329) and significantly declined after LOC (pre-LOC vs. post-LOC, p = 0.0094). For the emergence period, NAc DA release exhibited a noticeable increase during the initial period after recovery of consciousness (ROC) (anesthesia baseline vs. post-ROC, p = 0.0103; pre-ROC vs. post-ROC, p = 0.0086). Furthermore, the DA signals peaked rapidly upon the initiation of the burst wave and then gradually attenuated, indicating a positive correlation with the burst wave onset during burst suppression events.

Our findings revealed that NAc DA neurotransmitter signal dynamics correlate with different states of consciousness throughout sevoflurane anesthesia.