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Role of the 5-HT2C receptor in improving weight-supported stepping in adult rats spinalized as neonates
Journal article   Peer reviewed

Role of the 5-HT2C receptor in improving weight-supported stepping in adult rats spinalized as neonates

Tina Kao, Jed S Shumsky, Stacy Jacob-Vadakot, B Timothy Himes, Marion Murray and Karen A Moxon
Brain research, v 1112(1), pp 159-168
27 Sep 2006
DOI: https://doi.org/10.1016/j.brainres.2006.07.020
PMID: 16914121
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Spinal Cord Injuries - drug therapy Receptor, Serotonin, 5-HT2C - metabolism Motor Activity - drug effects Psychomotor Performance - physiology Behavior, Animal Dose-Response Relationship, Drug Receptor, Serotonin, 5-HT2C - physiology Drug Interactions Exercise Test - methods Up-Regulation - physiology Female Indoles - pharmacology Triglycerides - pharmacology Disease Models, Animal Animals, Newborn Rats gamma-Aminobutyric Acid - pharmacology Piperazines - therapeutic use Psychomotor Performance - drug effects Serotonin Antagonists - pharmacology Rats, Sprague-Dawley Weight-Bearing - physiology Serotonin Receptor Agonists - therapeutic use Animals Analysis of Variance Serotonin - metabolism Pyridines - pharmacology Spinal Cord Injuries - physiopathology gamma-Aminobutyric Acid - analogs & derivatives
Loss of descending serotonergic (5-HT) projections after spinal cord injury (SCI) contributes to motor deficits and upregulation of receptors on partially denervated serotonergic targets in the spinal cord. Serotonergic agonists acting on these upregulated receptors are potential therapeutic agents that could ameliorate motor deficits. However, modification of 5-HT receptors following complete spinal cord injury results in different effects by 5-HT2C receptor agonists and antagonists. For example, administration of 5-HT2C receptor agonists suppresses locomotor activity in normal animals, but enhances it in spinalized animals. In addition, administration of 5-HT2C receptor agonists does not induce activity-dependent hindlimb tremors in normal animals, but does induce them in spinalized animals. We therefore extended our previous work with the 5-HT2C receptor agonist 1-(m-chlorophenyl)-piperazine hydrochloride (mCPP), which enhances weight-supported stepping when administered to adult rats spinalized as neonates, to identify the optimal dose for improved weight-supported stepping with minimal side effects. In order to determine whether mCPP enhances weight-supported stepping after SCI is through activation of the 5-HT2C receptor, we performed the following experiments. We determined that stimulation of the 5-HT1A receptor did not contribute to this improvement in weight-support. We reversed the increase in mCPP-induced weight-supported stepping with SB 206,553, a 5-HT2C receptor antagonist. We also provide evidence for denervation-induced upregulation of 5-HT2C receptors in the injured spinal cord. Since mCPP does not have the behavioral toxicity associated with non-selective 5-HT2 receptor agonists, targeting the 5-HT2C receptor may have clinical relevance for the treatment of SCI.

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24 citations in Web of Science
24 citations in Scopus

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