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Role of spinal 5-HT2 receptor subtypes in quipazine-induced hindlimb movements after a low-thoracic spinal cord transection.
- Source :
-
The European journal of neuroscience [Eur J Neurosci] 2008 Dec; Vol. 28 (11), pp. 2231-42. Date of Electronic Publication: 2008 Nov 03. - Publication Year :
- 2008
-
Abstract
- A role of serotonin receptors (5-HTRs) in spinal rhythmogenesis has been proposed several years ago based mainly upon data showing that bath-applied 5-HT could elicit locomotor-like rhythms in in vitro isolated spinal cord preparations. Such a role was partially confirmed in vivo after revealing that systemically administered 5-HTR(2) agonists, such as quipazine, could induce some locomotor-like movements (LM) in completely spinal cord-transected (Tx) rodents. However, given the limited binding selectivity of currently available 5-HTR(2) agonists, it has remained difficult to determine clearly if one receptor subtype is specifically associated with LM induction. In situ hybridization, data using tissues from L1-L2 spinal cord segments, where critical locomotor network elements have been identified in mice, revealed greater 5-HTR(2A) mRNA levels in low-thoracic Tx than non-Tx animals. This expression level remained elevated for several days, specifically in the lateral intermediate zone, where peak values were detected at 1 week post-Tx and returned to normal at 3 weeks post-Tx. Behavioral and kinematic analyses revealed quipazine-induced LM in 1-week Tx mice either non-pretreated or pretreated with selective 5-HTR(2B) and/or 5-HTR(2C) antagonists. In contrast, LM completely failed to be induced by quipazine in animals pretreated with selective 5-HTR(2A) antagonists. Altogether, these results provide strong evidence suggesting that 5-HTR(2A) are specifically associated with spinal locomotor network activation and LM generation induced by quipazine in Tx animals. These findings may contribute to design drug treatments aimed at promoting locomotor function recovery in chronic spinal cord-injured patients.
- Subjects :
- Animals
Disease Models, Animal
Hindlimb innervation
Hindlimb physiopathology
Male
Mice
Motor Activity drug effects
Motor Activity physiology
Movement drug effects
Movement physiology
Nerve Net drug effects
Nerve Net metabolism
Paralysis drug therapy
Paralysis physiopathology
RNA, Messenger drug effects
RNA, Messenger metabolism
Receptor, Serotonin, 5-HT2A drug effects
Receptor, Serotonin, 5-HT2A genetics
Receptor, Serotonin, 5-HT2B drug effects
Receptor, Serotonin, 5-HT2B genetics
Receptor, Serotonin, 5-HT2B metabolism
Receptor, Serotonin, 5-HT2C drug effects
Receptor, Serotonin, 5-HT2C genetics
Receptor, Serotonin, 5-HT2C metabolism
Recovery of Function drug effects
Recovery of Function physiology
Serotonin metabolism
Serotonin Antagonists pharmacology
Serotonin Receptor Agonists pharmacology
Spinal Cord drug effects
Spinal Cord physiopathology
Spinal Cord Injuries drug therapy
Spinal Cord Injuries physiopathology
Synaptic Transmission drug effects
Synaptic Transmission physiology
Thoracic Vertebrae
Up-Regulation drug effects
Up-Regulation genetics
Paralysis metabolism
Quipazine pharmacology
Receptor, Serotonin, 5-HT2A metabolism
Spinal Cord metabolism
Spinal Cord Injuries metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-9568
- Volume :
- 28
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The European journal of neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19019202
- Full Text :
- https://doi.org/10.1111/j.1460-9568.2008.06508.x