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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
Tessler2, 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
Copyright © 1999 Society for Neuroscience 0270-6474/99/19146213-12$05.00/0
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