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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Up-regulation of 5-HT(2) 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-HT(2) receptors (5-HT(2)R) can potentiate the monosynaptic reflex. This study tested the hypothesis that increased expression of 5-HT(2)R 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-HT(2)R in this increased amplitude, dose-response studies were done with the selective antagonists mianserin or LY53857 and the 5-HT(2)R 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-HT(2)R antagonists reduced the H-reflex reflex amplitude with a significantly higher ID(50) compared to the uninjured controls. The 5-HT(2)R agonist DOI significantly increased reflex amplitude in contused but not control rats. Furthermore, while 5-HT immunoreactivity was similar, contused rats displayed increased 5-HT(2A)R immunoreactivity in plantar muscle motoneurons compared to uninjured controls. We conclude that increased expression of 5-HT(2)R is likely to be involved in the enhanced H-reflex that develops after contusive SCI.[1]

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