Propofol has an antiemetic effect that may be mediated by gamma -aminobutyr
ic acid (GABA) influences on the serotonin system, the mechanism of which i
s not known. We used three techniques, immunohistochemistry, High Performan
ce Liquid Chromatography, and electrophysiology, to define propofol's effec
ts on the rat's brainstem. Paired male Wistar rats received propofol, 20 mg
/kg/hr, or Intralipid (R) for 6 h. The brains were then subjected to immuno
histochemical analysis of serotonin. In a separate experiment after a propo
fol or Intralipid (R) infusion, cerebrospinal fluid (CSF) was extracted fro
m the fourth ventricle and analyzed for the amount of serotonin and 5-hydro
xyindoleacetic acid. Electrophysiological neuronal recordings were made in
the area postrema (AP) in response to propofol with and without a GABA or s
erotonin antagonist. Results showed that inununohistochemical staining for
serotonin in the propofol rats was significantly increased (28 +/- 12%) in
the dorsal raphe and decreased in the AP (17 +/- 6%) compared with control.
There were no significant changes in the isoflurane-anesthetized animals.
Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth vent
ricle at the level of the AP were significantly reduced by 63% and 36%, res
pectively. Both propofol and pentobarbital injections reduce AP neuronal ac
tivity, but only the propofol response was blocked by bicuculline, a GABA a
ntagonist. We conclude that the reduced levels of serotonin in the AP and t
he CSF may explain the antiemetic property of propofol. Propofol may also d
irectly act on AP neurons via a GABA, receptor to reduce their activity.