5‐HT₄ receptors in the hippocampus modulate rat locomotor activity

Abstract

In the present study, the ability of 5-hydroxytryptamine-4 (5-HT4) receptors in the hippocampus to enhance locomotor activity in rats was investigated by local infusion via microdialysis probes. The local infusion of 5-HT bilaterally into the striatum did not alter rat motor activity. The local infusion of 1.0 mM 5-HT into the bilateral hippocampus, but not lower doses, significantly increased motor activity as compared with the baseline values or the control rats. During the day hours (0700-1900, light on), the local infusion of either 5-HT4 agonist, 5-MeOT (100 microM) or mosapride (10 microM), but not in their lower concentrations, into the bilateral hippocampus significantly increased motor activity as compared with the baseline values or the control rats. Almost all increased motor activity was normal forward locomotion. This 5-MeOT-induced hyperlocomotion was completely reversed by the combined infusion of a 5-HT4 antagonist, either GR125487D (100 microM), SB204070 (100 microM) or RS23597-190 (100 microM). During the night hours (1900-0700, light off), the local infusion of either SB204070 (100 microM) or RS23597-190 (100 microM), but not in their lower concentrations, into the bilateral hippocampus significantly decreased rat motor activity and inhibited rat nocturnal hyperactivity. These hypoactivities during the night hours induced by 5-HT4 antagonist were reversed by the combined infusion of a 5-HT4 agonist, 5-MeOT (100 microM). The present study demonstrates that the serotonergic neurons projecting to the hippocampus, but not to the striatum, modulate rat locomotor activity by stimulating 5-HT4 receptors in the hippocampus.

Heritability, correlations and in silico mapping of locomotor behavior and neurochemistry in inbred strains of mice

“…Other studies have demonstrated similar correlations between dopamine metabolism and other locomotor behaviors (Gerber et al 2001;Hattori et al 1994;Miyamoto et al 2001;Murphy et al 2001). Alterations in serotonin can also influence locomotor behaviors (Brocco et al 2002;Muller et al 2003;Sabbe et al 2001;Takahashi et al 2002), as demonstrated by the modulation of the dopamine system by serotonin (Bonhomme et al 1995;Lucas et al 2000). Finally, only striatal turnover 2 (DOPAC þ HVA/DA) was significantly and positively correlated with the majority of behavioral slope measures.…”

“…2003; Sabbe et al . 2001; Takahashi et al . 2002), as demonstrated by the modulation of the dopamine system by serotonin (Bonhomme et al .…”

Chronic Fluoxetine Bidirectionally Modulates Potentiating Effects of Serotonin on the Hippocampal Mossy Fiber Synaptic Transmission

“…Hippocampal serotonin levels are positively correlated with animal activity (Linthorst et al, 1994). A systemic application of 5-HT 4 receptor antagonists reduces locomotor activity (Fontana et al, 1997) antagonists induces hyperlocomotion and hypolocomotion, respectively (Takahashi et al, 2002). The 5-HT-induced potentiation of the mossy fiber synaptic transmission was exclusively mediated by 5-HT 4 receptors ( Fig.…”

Does serotonin deficit mediate susceptibility to ADHD?

“…Takahashi et al, using a microdialysis probe showed that infusion of 5-HT in rat hippocampus but not striatum, significantly increased motor activity (Takahashi et al, 2002). Using 5-HTR4 agonists and antagonists it has been shown that the hyperactivity resulting from 5-HT infusion is modulated by 5-HTR4 in the hippocampus (Takahashi et al, 2002).…”