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Updated: May 10, 2026

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic
Yu-Wei Liu1, Wanhong Zuo, Jiang-Hong Ye
1Department of Anaesthesiology, UMDNJ, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA.
Background:
The cellular mechanisms underlying the sedative effect of general anesthetics are not completely understood. Accumulating evidence indicates that the ventrolateral preoptic area (VLPO) of the hypothalamus plays a critical role. The VLPO contains 2 major types of neurons, the noradrenalin-inhibited GABAergic projecting neurons (NA(-) neurons) and the noradrenalin-excited interneurons (NA(+) neurons) which are probably also γ-aminobutyric acid (GABA)-containing neurons. Our previous work suggests that NA(-) neurons are normally under the inhibitory control of NA(+) neurons. Previous studies also show that GABAergic agents including propofol activate GABAergic projecting neurons in the VLPO, which is believed to lead to the inhibition of the arousal-producing nuclei in the tuberomammillary nucleus and sedation. However, how propofol activates VLPO neurons remains unclear. We explored the possibility that propofol activates NA(-) neurons indirectly, by inhibiting GABAergic transmission including those from VLPO NA(+) neurons.
Methods:
Electrophysiological activities were recorded from VLPO cells in acute brain slices of rats.
Results:
Propofol facilitates the discharges of NA(-) neurons and reduces the frequency, but not the amplitude of spontaneous GABAergic inhibitory postsynaptic currents in NA(-) neurons. Conversely, propofol suppressed the discharges of NA(+) neurons.
Conclusion:
Propofol excites VLPO NA(-) neurons by reducing GABAergic transmission, at least in part by inhibiting VLPO NA(+) neurons. This may be a critical mechanism contributing to propofol-induced sedation.
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