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The Journal of Neuroscience, July 15, 1999, 19(14):6213-6224

Direct Agonists for Serotonin Receptors Enhance Locomotor Function in Rats that Received Neural Transplants after Neonatal Spinal Transection

Duckhyun Kim², V. Adipudi², M. Shibayama², Simon Giszter², Alan Tessler^{2, 3, 4}, Marion Murray², and Kenny J. Simansky¹

Departments of ¹ Pharmacology, ² Neurobiology and Anatomy, ³ Neurology, and ⁴ the VA Medical Service, MCP Hahnemann University, Philadelphia, Pennsylvania 19129

We analyzed whether acute treatment with serotonergic agonists would improve motor function in rats with transected spinal cords (spinal rats) and in rats that received transplants of fetal spinal cord into the transection site (transplant rats). Neonates received midthoracic spinal transections within 48 hr of birth; transplant rats received fetal (embryonic day 14) spinal 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 developed better weight-supported stepping than spinal rats. Systemic administration of two directly acting agonists for serotonergic 5-HT₂ receptor subtypes, quipazine and (+/)-1-[2,5]-dimethoxy-4-iodophenyl-2-aminopropane), further increased weight-supported stepping in transplant rats. The improvement was dose-dependent and greatest in rats with poor to moderate baseline weight support. In contrast, indirectly acting serotonergic agonists, which block reuptake of 5-HT (sertraline) or release 5-HT and block its reuptake (D-fenfluramine), failed to enhance motor function. Neither direct nor indirect agonists significantly improved locomotion in spinal rats as a group, despite equivalent upregulation of 5-HT₂ receptors in the lumbar ventral horn of lesioned rats with and without transplants. The distribution of immunoreactive serotonergic fibers within and caudal to the transplant did not appear to correspond to restoration of motor function. Our results confirm our previous demonstration that transplants improve motor performance in spinal rats. Additional stimulation with agonists at subtypes of 5-HT receptors produces a beneficial interaction with transplants that further improves motor competence.

Key words: spinal cord injury; transection; fetal transplant; serotonin agonists; locomotion; kinematics

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19146213-12$05.00/0

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