Serotonin refines the locomotor-related alternations in the in vitro neonatal rat spinal cord.
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.
Pearlstein
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E
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
Ben Mabrouk
F
F
Pflieger
J F
JF
Vinay
L
L
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
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