Abstract
Generation of the unconsciousness associated with arousal during the initial stage of anesthesia by midazolam is critical for general anesthesia, however, the exact mechanism remains unknown. Here, firstly, we found that the destruction of noradrenergic neurons in the locus coeruleus (LCNE) could prolong the emergence time of midazolam-induced anesthesia. Secondly, the same results were found by activation of the noradrenergic pathway between the LC and the ventrolateral preoptic nucleus (VLPO) using optogenetics and chemogenetics approaches, respectively. Thirdly, this effect was mediated by α1 and β adrenergic receptors rather than α2 adrenergic receptors in the VLPO. Moreover, the noradrenergic pathway to modulate the arousal between the LC and VLPO was controlled by GABAA receptors in the LC and VLPO in our models. Our data demonstrate that activation of the NEergic pathway between the LC and VLPO can promote arousal to prevent delayed recovery from midazolam-induced anesthesia.
Competing Interest Statement
The authors have declared no competing interest.