Serotonergic neurons in the dorsal raphe nucleus mediate the arousal-promoting effect of orexin during isoflurane anesthesia in male rats

Yang, Chunmei; Zhang, Lina; Hao, Haizhi; Ran, Mingzi; Li, Jiannan; Dong, Hailong

doi:10.1016/j.npep.2019.03.004

Cited by 32 publications

(25 citation statements)

References 33 publications

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“…Indeed, activation of DRN 5‐HT accelerated recovery to consciousness, and inhibition delayed the emergence period. These results further extended our findings that wake‐promoting neuropeptide, orexin, could activate DRN 5‐HT neurons to facilitate the emergence from general anesthesia 20 …”

Section: Discussionsupporting

confidence: 85%

“…These results further extended our findings that wake‐promoting neuropeptide, orexin, could activate DRN 5‐HT neurons to facilitate the emergence from general anesthesia. 20 …”

Section: Discussionmentioning

confidence: 99%

“…Recently, an elaborately performed study demonstrated the bidirectional role of serotonergic system in the maintenance of sleep homeostasis and the regulation of sleep/wake cycle 19 . We previously reported that orexin facilitated emergence from isoflurane anesthesia partially through activating 5‐HT neurons in the DRN, but there is no direct evidence supporting the casual effect of DRN 5‐HT neurons themselves on the effect of general anesthesia 20 …”

Section: Introductionmentioning

confidence: 99%

“… 19 We previously reported that orexin facilitated emergence from isoflurane anesthesia partially through activating 5‐HT neurons in the DRN, but there is no direct evidence supporting the casual effect of DRN 5‐HT neurons themselves on the effect of general anesthesia. 20 …”

Section: Introductionmentioning

confidence: 99%

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Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia

Ouyang

et al. 2021

CNS Neurosci Ther

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Aims General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating. Methods Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst‐suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods. Results We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5‐HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5‐HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons. Conclusion Our results demonstrate that 5‐HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5‐HT 1A and 2C receptors.

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Section: Discussionsupporting

confidence: 85%

“…These results further extended our findings that wake‐promoting neuropeptide, orexin, could activate DRN 5‐HT neurons to facilitate the emergence from general anesthesia. 20 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia

Ouyang

et al. 2021

CNS Neurosci Ther

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“…45,46 A binary series was applied for BSR calculation, with the value being 1 if the transformed signal of EEG was outside the defined threshold and being 0 if it was within the threshold. The minimum duration of burst and suppression periods was set to 0.5 s. 20,45,47 BSR was calculated as the percentage of suppression at 30 s before, during, or after photostimulation of NAc D1R neurons.…”

Section: Eeg/emg Analysismentioning

confidence: 99%

Nucleus accumbens neurons expressing dopamine D1 receptors modulate states of consciousness in sevoflurane anesthesia

Bao

Pan

et al. 2021

Current Biology

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Application of quinpirole in the paraventricular thalamus facilitates emergence from isoflurane anesthesia in mice

Yang

Zhang

et al. 2020

Brain and Behavior

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Background and Purpose Dopamine is well‐known to contribute to emergence from anesthesia. Previous studies have demonstrated that the paraventricular thalamus (PVT) in the midline nuclei is crucial for wakefulness. Moreover, the PVT receives dopaminergic projections from the brainstem. Therefore, we hypothesize that the dopaminergic signaling in the PVT plays a role in emergence from isoflurane anesthesia. Methods We used c‐Fos immunohistochemistry to reveal the activity of PVT neurons in three groups: The first group (iso + EM ‐ ) underwent the anesthesia protocol and was sacrificed before emergence. The second group (iso + EM + ) underwent passive emergence from the same anesthesia protocol. The last group (oxy + ) received oxygen. D2‐like agonist quinpirole (2 or 4 mM) or D2‐like antagonist raclopride (2 or 5 mM) was microinjected into the PVT, and their effects on emergence and induction time were analyzed. Surface cortical electroencephalogram (EEG) recordings were used to explore the effects of quinpirole injection into the PVT on cortical excitability during isoflurane anesthesia. The activity of PVT neurons after quinpirole injection was assessed by c‐Fos immunohistochemistry. Results The number of c‐Fos‐positive nuclei for the iso + EM + group was significantly higher than the oxy + and iso + EM ‐ groups. Application of quinpirole (4 mM) into the PVT shortened emergence time compared with the saline group ( p < .01). In contrast, administration of raclopride (2 mM) delayed emergence time ( p < .05). Neither quinpirole nor raclopride exerted an effect on induction time. EEG analyses showed that quinpirole (4 mM) decreased the burst suppression ratio during isoflurane anesthesia ( p < .01). The number of c‐Fos‐positive nuclei for the quinpirole (4 mM) group was significantly higher than saline group ( p < .01). Conclusions Our findings suggest that the activity of PVT neurons is enhanced after emergence from anesthesia, and the dopaminergic signaling in the PVT may facilitate emergence from isoflurane anesthesia.

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Serotonergic neurons in the dorsal raphe nucleus mediate the arousal-promoting effect of orexin during isoflurane anesthesia in male rats

Cited by 32 publications

References 33 publications

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia

Nucleus accumbens neurons expressing dopamine D1 receptors modulate states of consciousness in sevoflurane anesthesia

Application of quinpirole in the paraventricular thalamus facilitates emergence from isoflurane anesthesia in mice

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