The effects of propofol in the area postrema of rats

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.