Propofol Causes Consciousness Loss by Affecting GABA-A Receptor in the Nucleus Basalis of Rats.

Yunlong Xing,Zinan Li,Kai Li,Yuan Jiao

doi:10.1155/2020/9370891

Abstract

Objective Propofol is a classical anesthetic and induces consciousness loss, and gamma-aminobutyric-acid-type-A (GABA-A) receptor is its target. Righting reflex is associated with conscious response. The nucleus basalis (NB) acts as a major relay between the reticular activating system and the frontal cortex (FC). Propofol may mediate righting reflex by affecting GABA-A receptor in NB. Methods Fifty male SD rats (250-350 g) were divided into parts I and II. In part I, 20 male SD rats were randomly divided into control group (CG) and NB-lesion group (NG, ibotenic acid-induced NB lesion). In part II, 30 male SD rats were treated with saline (0.9% NaCl, SG group), muscimol (a GABA-A receptor agonist, MG group), and gabazine (a GABA-A receptor antagonist, GG group) in NB, respectively. Two weeks later, the activity of the rats was measured between CG and NG groups. The rats were intravenously injected with propofol (50 mg/kg/h) to test the time of loss of righting reflex (LORR) in all rats. When LORR occurred, the rats received single administration of propofol (12 mg/kg) to measure the time of return of righting reflex (RORR). Electroencephalogram (EEG) activity of the frontal cortex (FC) was recorded. Results The numbers of NB neurons were reduced by 44% in the NG group compared to the CG group (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (p < 0.05) whereas the activity of rats was reduced a little in the NG group when compared with the CG group, but the statistical difference was insignificant (Conclusions The unilateral NB lesion increased the recovery time and FC delta power, and the NB region might be involved in the emergence after propofol administration. Propofol plays a crucial role for causing conscious loss by affecting GABA-A receptor in NB.

Highlights

Propofol is a classical intravenous anesthetic and can induce consciousness loss, and the mechanism remains unclear
Compared with the control group, the number of nucleus basalis (NB) cells was reduced by 44% (Figure 1(e), p < 0:05), suggesting the injury NB model was successfully established
After 2-week establishment of the NB-lesion model, no significant differences were observed between NB- and sham-lesioned rats the total activities in the control group (CG) group were slightly lower than those in the NG group (Figure 2(a))

Summary

Introduction

Propofol is a classical intravenous anesthetic and can induce consciousness loss, and the mechanism remains unclear. Basal forebrain (BF) is located in the anterior aspect of the hypothalamus and the ventral medial aspect of the striatum. The injection of fluorescent protein in BF, which tracks the fiber projection of cholinergic neurons, showed that cholinergic nerve fibers are densely projected to the frontal cortex (FC) [2]; the activation of the neurons can increase the expression of c-fos protein in FC neurons [3]. Cholinergic neurons are mainly distributed in NB, which can accept nerve projections from the hypothalamus and brainstem awakening nerve nucleus while emitting dense projections to the FC4. Studies have shown that the acetylcholine content of the cerebral cortex derived from NB is higher than that of the slow-wave sleep in the awake and rapid eye movement sleep, indicating that NB cholinergic neurons play an important role in maintaining wakefulness and regulating sleep-wake cycles [4]

Methods

Results

Discussion

Conclusion