Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury.
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.
Lee
Jae K
JK
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
Johnson
Christopher S
CS
Wrathall
Jean R
JR
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003288:Contusions / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006181:H-Reflex / Q000502:physiology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008803:Mianserin / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D000662:Amphetamines; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008803:Mianserin; C032663:LY 53857; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine