title: Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic inhibition.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesiology, UMDNJ, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Liu
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Ye
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects* / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine; D015742:Propofol