Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic inhibition

Yu Wei Liu, Wanhong Zuo, Jiang Hong Ye

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalAnesthesia and analgesia
Volume117
Issue number2
DOIs
StatePublished - Aug 2013

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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