The time course of serotonin 2C receptor expression after spinal transection of rats: an immunohistochemical study

In the spinal cord serotonin (5-HT) systems modulate the spinal network via various 5-HT receptors. Serotonin 2A receptor and serotonin 2C receptor (5-HT2A and 2C receptors) are likely the most important 5-HT receptors for enhancing the motoneuron excitability by facilitating the persistent inward current (PIC), and thus play an important role for the pathogenesis of spasticity after spinal cord injury. In conjunction with our 5-HT2A receptor study, using a same sacral spinal transection rat model we have in this study examined 5-HT2C receptor immunoreactivity (5-HT2CR-IR) changes at seven different time intervals after spinal injury. We found that 5-HT2CR-IR was widely distributed in different regions of the spinal gray matter and was predominantly located in the neuronal somata and their dendrites although it seemed also present in axonal fibers in the superficial dorsal horn. 5-HT2CR-IR in different regions of the spinal gray matter was seen to be increased at 14days after transection (with an average ∼1.3-fold higher than in sham-operated group) but did not reach a significant level until at 21days (∼1.4-fold). The increase sustained thereafter and a plateau level was reached at 45days (∼1.7-fold higher), a value similar as that at 60days. When 5-HT2CR-IR analysis was confined to the ventral horn motoneuron somata (including a proportion of proximal dendrites) a significant increase was not detected until 45days post-operation. 5-HT2CR upregulation in the spinal gray matter is confirmed with Western blot in the rats 60days post-operation. The time course of 5-HT2CR upregulation in the spinal gray matter and motoneurons was positively correlated with the development of tail spasticity (clinical scores). This indicates that 5-HT2CR is probably an important factor underlying this pathophysiological development by increasing the excitability of both motoneurons and interneurons.