Contribution of spinal 5-HT1Aand 5-HT7receptors to locomotor-like movement induced by 8-OH-DPAT in spinal cord-transected mice

Autor:	Daniel Lévesque, Nicolas P. Lapointe, Éric Landry, Peter B. Hedlund, Claude Rouillard, Pierre A. Guertin
Rok vydání:	2006
Předmět:	Male Agonist Serotonin medicine.medical_specialty medicine.drug_class Biology Efferent Pathways Synaptic Transmission Mice chemistry.chemical_compound In vivo Internal medicine medicine Animals Receptor Spinal cord injury Spinal Cord Injuries Mice Knockout 8-Hydroxy-2-(di-n-propylamino)tetralin 8-OH-DPAT musculoskeletal neural and ocular physiology General Neuroscience Antagonist Recovery of Function Spinal cord medicine.disease Nerve Regeneration Serotonin Receptor Agonists Mice Inbred C57BL Disease Models Animal Endocrinology medicine.anatomical_structure Spinal Cord chemistry Receptors Serotonin Receptor Serotonin 5-HT1A Serotonin Antagonists Neuroscience Locomotion
Zdroj:	European Journal of Neuroscience. 24:535-546
ISSN:	1460-9568 0953-816X
DOI:	10.1111/j.1460-9568.2006.04917.x
Popis:	Growing evidence from in vitro studies suggests that spinal serotonin (5-HT) receptor subtypes 5-HTR(1A) and 5-HTR(7) are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesis in vivo remains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a potent and selective 5-HTR(1A/7) agonist, in mice spinal cord transected at the low-thoracic level (Th9/10). The results show that 8-OH-DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5-HTR(1A) antagonists, WAY100,135 or WAY100,635, displayed significantly less 8-OH-DPAT-induced movement. A similar reduction of 8-OH-DPAT-induced movements was found in animals pretreated with SB269970, a selective 5-HTR(7) antagonist. Moreover, a near complete blockade of 8-OH-DPAT-induced movement was obtained in wild-type mice pretreated with 5-HTR(1A) and 5-HTR(7) antagonists, and in 5-HTR(7)-/- mice pretreated with 5-HTR(1A) antagonists. Overall, these results clearly demonstrate that 8-OH-DPAT potently induces locomotor-like movement in the previously paralysed hindlimbs of low-thoracic-transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesis in vivo.
Databáze:	OpenAIRE
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