Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Exp Neurol. 2007 Feb;203(2):502-11. doi: 10.1016/j.expneurol.2006.09.003. Epub 2006 Oct 23.


The amplitude of the H-reflex increases chronically after incomplete SCI and is associated with the development of exaggerated hindlimb reflexes. Although the mechanism for this increased H-reflex is not clear, previous studies have shown that pharmacological activation of the 5-HT2 receptors (5-HT2R) can potentiate the monosynaptic reflex. This study tested the hypothesis that increased expression of 5-HT2R on motoneurons is involved in increased H-reflex amplitude after a standardized clinically relevant contusive SCI. Adult female rats were subjected to contusion, complete surgical transection, or a T8 laminectomy only. At 4 weeks after surgery, H-reflex recordings from the hindpaw plantar muscles of contused rats showed twice the amplitude of that in laminectomy controls or transected rats. To probe the role of 5-HT2R in this increased amplitude, dose-response studies were done with the selective antagonists mianserin or LY53857 and the 5-HT2R agonist (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). The drugs were intrathecally infused into the lumbar cord while recording the H-reflex. Mianserin did not have any significant effects on the H-reflex after transection, consistent with the loss of distal serotonergic innervation. After contusion, both 5-HT2R antagonists reduced the H-reflex reflex amplitude with a significantly higher ID50 compared to the uninjured controls. The 5-HT2R agonist DOI significantly increased reflex amplitude in contused but not control rats. Furthermore, while 5-HT immunoreactivity was similar, contused rats displayed increased 5-HT2AR immunoreactivity in plantar muscle motoneurons compared to uninjured controls. We conclude that increased expression of 5-HT2R is likely to be involved in the enhanced H-reflex that develops after contusive SCI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamines / pharmacology
  • Animals
  • Contusions / metabolism*
  • Ergolines / pharmacology
  • Female
  • H-Reflex / physiology*
  • Immunohistochemistry
  • Injections, Spinal
  • Mianserin / pharmacology
  • Motor Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / biosynthesis*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord Injuries / metabolism*
  • Up-Regulation / physiology


  • Amphetamines
  • Ergolines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Mianserin
  • LY 53857
  • 4-iodo-2,5-dimethoxyphenylisopropylamine