Opposing roles for 5‐HT_1B and 5‐HT₃ receptors in the control of 5‐HT release in rat hippocampus in vivo

Abstract

1 Intracerebral microdialysis was used to determine whether 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of rats anaesthetized with chloral hydrate was modulated by 5-HT3 receptors. 2 It was confirmed that 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-lH-indole (RU 24969), a selective 5-HTB receptor agonist, decreased 5-HT release in a dose-and concentration-related manner when administered i.p. (1 and 5 mg kg-') or via the dialysis probe (0.1 and 1 ftM) respectively. The effect of RU 24969 infusion (1I JM) was attenuated by concurrent infusion of metitepine (10 JiM) into the hippocampus. 3 When infused into the hippocampus for 15 min, the selective 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT; 0.1-10O tM) increased dialysate 5-HT levels in a concentrationrelated manner; an effect which was abolished by concurrent infusion of 3-tropanyl-3,5-dichlorobenzoate (1 ELM, MDL 72222), a selective 5-HT3 antagonist.4 MDL 72222 had no effects on hippocampal 5-HT release when administered via the dialysis probe (1 or 10 tiM).5 The data show that 5-HT3 and 5-HTIB receptors have opposing roles in the control of 5-HT release in the hippocampus, with 5-HT3 receptors facilitating and 5-HTlB receptors inhibiting 5-HT efflux, respectively. They also indicate that the facilitatory 5-HT3 receptors are not tonically activated.

Functional characterization of a 5‐HT3 receptor which modulates the release of 5‐HT in the guinea‐pig brain

“…The relative potency order of the antagonists observed in the present study relates fairly well to the data obtained in the guinea-pig vagus preparation (see Hoyer, 1990 (Ge et al, 1991;Martin et al, 1992). It is noteworthy that in the latter report, 2-methyl-5-HT enhanced the extracellular level of 5-HT, and this enhancing effect was prevented by MDL 72222 (Martin et al, 1992). However, given the capacity of this 5-HT3 receptor to desensitize rapidly and the markedly different quantitative effect it can exert over a very narrow range of 5-HT release, it would seem that microdialysis may not be ideally suited to study its influence on the modulation of 5-HT release in vivo.…”

“…Nethertheless, R-and S-zacopride were effective down to a concentration of 10 nM. The relative potency order of the antagonists observed in the present study relates fairly well to the data obtained in the guinea-pig vagus preparation (see Hoyer, 1990 (Ge et al, 1991;Martin et al, 1992). It is noteworthy that in the latter report, 2-methyl-5-HT enhanced the extracellular level of 5-HT, and this enhancing effect was prevented by MDL 72222 (Martin et al, 1992).…”

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

“…Later, it was reported that 5-HT suppresses long term potentiation (LTP) in hippocampal slices by preventing the activation of NMDA receptors and the enhancement of AMPA-mediated currents that lead to LTP induction [171]. The hippocampus contains several subtypes of serotonin receptors, namely 5-HT 1A [160,174], 5HT 1B [4,130], 5-HT 2 [17,28], 5-HT 3 [116,132], 5-HT 4 [5,160], 5-HT 6 and 5-HT 7 [73], many of which modulate glutamate-mediated transmission acting at different levels. In the CA1 region, pre-synaptic 5-HT 1A receptors reduce glutamate release from Schaffer collaterals to CA1 pyramidal neurons [162] (Fig.…”

5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story?

“…In spite of this promising perspective, experiments to demonstrate 5-HT 3 receptor-mediated 5-HT release in the amygdala do not appear to have been carried out. By contrast, a 5-HT 3 receptor-mediated enhancement of 5-HT release has been reported from other brain regions, for example, hippocampus, frontal cortex, hypothalamus, and raphé nucleus [22][23][24][25] . However, the presence of 5-HT 3 receptors on serotonergic nerve endings in these brain regions has not been demonstrated thus far.…”