title: Serotonin refines the locomotor-related alternations in the in vitro neonatal rat spinal cord.
abstract: Serotonergic projections from raphe nuclei arrive in the lumbar enlargement of the spinal cord during the late fetal period in the rat, a time window during which the locomotor-related left/right and flexor/extensor coordinations switch from synchrony to alternation. The goal of the present study was to investigate the role played by serotonin (5-HT) in modulating the left/right and flexor/extensor alternations. Fictive locomotion was induced by bath application of N-methyl-D,L-aspartate (NMA) in the in vitro neonatal rat spinal cord preparation. By means of cross-correlation analysis we demonstrate that 5-HT, when added to NMA, improves left/right and flexor/extensor (recorded from the 3rd and 5th lumbar ventral roots, respectively) alternations. This effect was partly reproduced by activation of 5-HT(2A/2C) receptors. We then tested the contribution of endogenous 5-HT to NMA-induced fictive locomotion. Reducing the functional importance of endogenous 5-HT, either by inhibiting its synthesis with daily injections of p-chloro-phenylalanine (PCPA), starting on the day of birth, or by application of ketanserin (a 5-HT(2) receptor antagonist) or SB269970 (a 5-HT(7) receptor antagonist), disorganized the NMA-induced locomotor pattern. This pattern was restored in PCPA-treated animals by adding 5-HT to the bath. Blocking 5-HT(7) receptors disorganized the locomotor-like rhythm even in the absence of electrical activity in the brain stem, suggesting that NMA applied to the spinal cord does not cause 5-HT release by activating a spino-raphe-spinal loop. These results demonstrate that 5-HT is critical in improving the locomotor-related alternations in the neonatal rat.
authors.affiliation: Laboratoire Plasticité et Physio-Pathologie de la Motricité (PM), CNRS & Université de la Méditerranée, UMR 6196, CNRS, 31 Chemin Joseph Aiguier, F-13402 Marseille Cedex 20, France. pearlst@dpm.cnrs-mrs.fr
authors.forename: E
authors.initials: E
authors.lastname: Pearlstein
authors.forename: F
authors.initials: F
authors.lastname: Ben Mabrouk
authors.forename: J F
authors.initials: JF
authors.lastname: Pflieger
authors.forename: L
authors.initials: L
authors.lastname: Vinay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D007839:Functional Laterality; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013223:Statistics as Topic; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D016202:N-Methylaspartate; D007650:Ketanserin; D010134:Fenclonine