Direct agonists for serotonin receptors enhance locomotor function in ratsthat received neural transplants after neonatal spinal transection

We analyzed whether acute treatment with serotonergic agonists would improv e motor function in rats with transected spinal cords (spinal rats) and in rats that received transplants of fetal spinal cord into the transection si te (transplant rats). Neonates received midthoracic spinal transections wit hin 48 hr of birth; transplant rats received fetal (embryonic day 14) spina l cord grafts at the time of transection. At 3 weeks, rats began 1-2 months of training in treadmill locomotion. Rats in the transplant group develope d better weight-supported stepping than spinal rats. Systemic administratio n of two directly acting agonists for serotonergic 5-HT2 receptor subtypes, quipazine and (+/-)-1-[2,5]-dimethoxy-4-iodophenyl-2-aminopropane), furthe r increased weight-supported stepping in transplant rats. The improvement w as dose-dependent and greatest in rats with poor to moderate baseline weigh t support. In contrast, indirectly acting serotonergic agonists, which bloc k reuptake of 5-HT (sertraline) or release 5-HT and block its reuptake (D-f enfluramine), failed to enhance motor function. Neither direct nor indirect agonists significantly improved locomotion in spinal rats as a group, desp ite equivalent upregulation of 5-HT2 receptors in the lumbar ventral horn o f lesioned rats with and without transplants. The distribution of immunorea ctive serotonergic fibers within and caudal to the transplant did not appea r to correspond to restoration of motor function. Our results confirm our p revious demonstration that transplants improve motor performance in spinal rats. Additional stimulation with agonists at subtypes of 5-HT receptors pr oduces a beneficial interaction with transplants that further improves moto r competence.