Serotonin-induced inhibition of locomotor rhythm of the rat isolated spinal cord is mediated by the 5–HT1 receptor class

Abstract

The neurotransmitter serotonin (5-HT) induces rhythmic motor patterns (¢ctive locomotion) of the neonatal rat spinal cord in vitro; this is a useful experimental model to study the generation of a motor programme at exclusively spinal level. Nevertheless, 5-HT slows down the ¢ctive locomotion typically elicited by activation of NMDA glutamate receptors, suggesting a complex action of this monoamine. By means of electrophysiological recordings from multiple ventral roots we demonstrated that the decrease caused by 5-HT in NMDA-induced periodicity was dose-dependent, enhanced after pharmacological blocking of 5-HT 2 excitatory receptors, and imitated by pharmacological agonists of the 5-HT 1 receptor family. Selective blockers of the 5-HT 1A or 5-HT 1B/D receptor classes, either alone or in combination, largely (but not completely) attenuated this inhibitory action of 5-HT. It is concluded that the principal inhibitory action of 5-HT on the spinal locomotor network was mediated by certain subtypes of the 5-HT 1 receptor class, which tends to oppose the 5-HT 2 receptor-mediated excitation of the same network.

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

“…NMDA channels and 5HT receptors are integral in the regulation of spinal reflexes and rhythmic motor pathways (13,14,(75)(76)(77). Activation of 5HT2C receptors induces long lasting reflexes (78), and after spinal cord injury, locomotion in rats requires constitutive activity of 5HT2C receptors (79).…”

Dopaminergic Modulation of Spinal Neuronal Excitability

“…An important caveat is that DA may not have similar actions in different cells in the ventral horn. Heterogeneity of actions is a hallmark of monoaminergic modulatory actions in the spinal cord (Kemnitz, 1997;Beato and Nistri, 1998;Rekling et al, 2000;Schmidt and Jordan, 2000;Gordon and Whelan, 2006), and there is reason to suspect that DA may also have different effects on different classes of ventral horn neurons depending on DA receptor distribution (Dubois et al, 1986;Maitra et al, 1993;Seth et al, 1993;Levant and McCarson, 2001). In other regions of the brain, DA increases EPSCs in layer II-III pyramidal neurons (GonzalezIslas and Hablitz, 2003) in rat prefrontal cortex but decreases EPSCs in the nucleus of the solitary tract (Kline et al, 2002).…”

Ontogenic Changes of the Spinal GABAergic Cell Population Are Controlled by the Serotonin (5-HT) System: Implication of 5-HT1Receptor Family

“…In the adult spinal cord, 5-HT 1 and 5-HT 2 receptors are involved in (1) the modulation of motor networks (Jackson and White, 1990;Cazalets et al, 1992;Beato and Nistri, 1998), (2) the modulation of motoneuronal excitability (Takahashi and Berger, 1990;Wang and Dun, 1990), and (3) spinal cord recovery (Antri et al, 2003;Norreel et al, 2003). The role of these receptors in the maturation of embryonic networks is poorly understood.…”