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

Jae K. Lee, Christopher S. Johnson, Jean R. Wrathall

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)502-511
Number of pages10
JournalExperimental neurology
Volume203
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • 5-HT receptor
  • Contusion
  • H-reflex pharmacology
  • Hyperreflexia
  • Lumbar spinal cord
  • MASCIS
  • Monosynaptic Ia afferent reflex
  • Serotonin
  • Spasticity
  • Transection

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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