The serotonergic 5-HT2C agonist m-chlorophenylpiperazine increases weight-supported locomotion without development of tolerance in rats with spinal transections

Abstract

The direct serotonergic agonist, m-chlorophenylpiperazine (m-CPP), displays high efficacy at 5-HT2C receptors. Systemic administration of m-CPP increased dramatically the percentage of weight-supported steps made on a treadmill by rats with complete midthoracic spinal transections. The improvement in motor function occurred in rats with grafts of fetal spinal cord into the site of transection (transplant rats) and in spinal rats without grafts (spinal rats), m-CPP produced a therapeutic action with its first administration and after 14 single daily injections. In contrast, the serotonin and norepinephrine reuptake inhibitor, chlorimipramine (CMI), failed to enhance weight support during 21 days of treatment. The results imply that stimulating directly 5-HT2C receptors restores postural support after spinal injury. Thus, 5-HT2C agonists are candidates for treating spinal patients chronically without the development of tolerance. © 2001 Academic Press.