Role of cortical reorganization on the effect of 5-HT pharmacotherapy for spinal cord injury.

Cortical reorganization or expansion of the intact cortical regions into the deafferented cortex after complete spinal transection in neonatally spinalized rats was shown to be essential for increases in weight-supported stepping at adulthood. The novel somatotopic organization identified in these animals can be induced by exercise or spinal transplants that bridge the site of injury. However, the role of cortical reorganization in increased weight-supported (WS) stepping after pharmacotherapy is unknown. For the neonatally spinalized rat model, the 5-HT(2C) receptor agonist 1-(m-chlorophenyl)-piperazine hydrochloride (mCPP) increases the number of WS steps taken when administered to adult rats spinalized as neonates (mCPP+) though not all animals showed this effect (mCPP-). Since no differences in the behavior of the animals off-drug has been demonstrated, it is unclear why acute administration of 5-HT affects only a subset of animals. One possibility is that differences in cortical organization between mCPP+ and mCPP- may contribute to the differences in the functional effect of mCPP. To test this, we recorded from single neurons in the deafferented hindlimb sensorimotor cortex during passive sensory stimulation of the cutaneous surface of the forepaws and during active sensorimotor stimulation of the forepaws while the animals locomoted on a motorized treadmill. Our results show that neurons recorded from mCPP+ animals increased their responsiveness to both passive and active stimulation off-drug in comparison to neurons from mCPP- animals. These data suggest that differences in the cortical organization of mCPP+ compared to mCPP- animals may be at least partially responsible for the effect of a 5-HT(2C) receptor agonist on functional outcome.