Effect of 5-HT2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism

Psychopharmacology (Berl). 1999 Jan;141(2):162-8. doi: 10.1007/s002130050820.


This study examined the role of the serotonin 5-HT2 receptor in motor function by examining the effect of antagonists on the motor performance of a cranial nerve reflex, the nictitating membrane (NM) reflex of the rabbit. The NM reflex was elicited by varying intensities of a tactile stimulus and the magnitudes of the elicited responses were measured at each intensity. Dose-response curves were obtained for the effects of several 5-HT2 receptor antagonists on response magnitude. d-Bro-molysergic acid diethylamide (BOL), LY-53,857 and ketanserin had no significant effect on the magnitude of the NM reflex, indicating that they are neutral antagonists. However, the 5-HT2 receptor antagonists ritanserin, MDL-11,939 and mianserin produced a significant reduction in response magnitude with no significant effects on response frequency, suggesting that they were acting as inverse agonists at the 5-HT2 receptor. The reduction in reflex magnitude produced by mianserin (10 micromol/kg) was fully blocked by BOL (5.8 micromol/kg), supporting the conclusion that mianserin was producing a reduction in reflex magnitude through an effect at the 5-HT2 receptor. The occurrence of inverse agonism suggests the possible existence of constitutive activity in vivo. We conclude that the 5-HT2 receptor (either 2A or 2C) plays an important role in motor function, perhaps by providing a tonic influence on motor systems.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cranial Nerves / drug effects*
  • Cranial Nerves / physiology
  • Ergolines / pharmacology
  • Female
  • Ketanserin / pharmacology
  • Lysergic Acid Diethylamide / analogs & derivatives
  • Lysergic Acid Diethylamide / pharmacology
  • Male
  • Mianserin / pharmacology
  • Piperidines / pharmacology
  • Rabbits
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology
  • Reflex / drug effects*
  • Reflex / physiology
  • Ritanserin / pharmacology
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*


  • Ergolines
  • Piperidines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol
  • Ritanserin
  • Mianserin
  • Lysergic Acid Diethylamide
  • Ketanserin
  • 2-bromolysergic acid diethylamide
  • LY 53857