5-Hydroxytryptamine3 receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius

doi:10.1016/0304-3940(95)11564-5

Neuroscience Letters

Volume 191, Issues 1–2, 19 May 1995, Pages 75-78

https://doi.org/10.1016/0304-3940(95)11564-5 Get rights and content

Abstract

In vivo microdialysis was employed to measure release of endogenous l-glutamate (GLU) and l-aspartate (ASP) in the medial nucleus tractus solitarius of urethane anaesthetised rats. Basal extracellular levels of these amino acids were stable following a 90 min equilibration period (6.3 ± 0.24 and 3.4 ± 0.6 pmol/20 μl sample of GGLU and ASP, respectively). Basal levels of endogenous extracellular GLU and ASP were increased over 2-fold and 3-fold, respectively, following local administration of the selective 5-hydroxytryptamine (5-HT₃) receptor agonist phenylbiguanide (300 μM). Intracerebral administration of the selective 5-HT₃ receptor antagonist ondansetron (30 μM) blocked the effect of phenylbiguanide on GLU release whilst the effect on ASP was variable and complex. These data suggest that 5-HT₃ receptor activation in the rat nucleus tractus solitarius can affect excitatory amino acid neurotransmission in this region of the medulla oblongata.

References (29)

J.M. Catelli et al.
GABAergic mechanisms in nucleus tractus solitarius alter blood pressure and vasopressin release
Brain Res.
(1987)
J. Ciriello
Brainstem projections of aortic baroreceptor afferent fibers in the rat
Neurosci. Lett.
(1983)
W.D. Dietrich et al.
The distribution of glutamate, GABA and aspartate in the nucleus tractus solitarius of the cat
Brain Res.
(1982)
S.R. Glaum et al.
5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro
Brain Res.
(1992)
A.R. Granata et al.
Release of [³H]l-glutamic acid (l-Glu) and [³H]d-aspartic acid (d-Asp) in the area of the nucleus tractus solitarius in vivo produced by stimulation of the vagus nerve
Brain Res.
(1983)
T. Kubo et al.
Evidence of N-methyl-d-aspartate receptor-mediated modulation of the aortic baroreceptor reflex in the rat nucleus tractus solitarii
Neurosci. Lett.
(1988)
A.J. Lawrence et al.
l-Glutamate as a neurotransmitter at baroreceptor afferents: evidence from in vivo microdialysis
Neuroscience
(1994)
N. Merahi et al.
Baroreceptor reflex inhibition induced by the stimulation of serotonin₃ receptors in the nucleus tractus solitarius of the rat
Neuroscience
(1992)
A. Nosjean et al.
Serotonergic projections from the nodose ganglia to the nucleus tractus solitarius: an immunohistochemical and double-labelling study in the rat
Neurosci. Lett.
(1990)
M.H. Perrone
Biochemical evidence that l-glutamate is a neurotransmitter of primary vagal afferent nerve fibers
Brain Res.
(1981)

B.P. Richardson et al.

The pharmacology and function of 5-HT₃ receptors

Trends Neurosci.

(1986)

A. Shvaloff et al.

Serotonin receptors in the rat nucleus tractus solitarii and cardiovascular regulation

Eur. J. Pharmacol.

(1986)

H.W.M. Steinbusch

Distribution of 5-HT-immunoreactivity in the central nervous system of the rat-cell bodies and terminals

Neuroscience

(1981)

R.E. Allchin et al.

Electrical stimulation of the vagus increases extracellular glutamate recovered from the nucleus tractus solitarii of the cat by in vivo microdialysis

Exp. Physiol.

(1994)

Cited by (44)

Ventral tegmental area serotonin 5-HT<inf>1A</inf> receptors and corticolimbic cFos/BDNF/GFAP signaling pathways mediate dextromethorphan/morphine anti-allodynia
2021, Physiology and Behavior
Citation Excerpt :
There are a large number of serotonergic inputs from the dorsal raphe (DR.) to the VTA which strongly promotes reward, and motivational function [61]. Serotonin (5-HT) has a modulatory role in glutamate transmission [62], especially in the brain areas controlling pain [63, 64]. The serotonergic modulatory effects on pain likely depend on the activated 5-HT receptor type and the action site.
The present study examined the role of ventral tegmental area (VTA) serotonergic 5HT_1A receptors in dextromethorphan/morphine-induced anti-allodynia and the possible changes of corticolimbic cFos, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) following the treatments.
The VTA cannulation and the chronic constriction of the sciatic nerve were performed in male Wistar rats. Flexion withdrawal thresholds to mechanical stimulation in the hind-limb were determined using von Frey hairs. The expressions of cFos, BDNF, and GFAP were evaluated using the Western blotting technique.
BDNF (in the hippocampus), and GFAP (in the targeted sites) levels were increased following neuropathic pain. Morphine administration induced an anti-allodynic effect with a decrease in the amygdala BDNF level. Dextromethorphan/morphine-induced anti-allodynia was accompanied by the decrease of hippocampus/amygdala/PFC GFAP and amygdala cFos expressions. The PFC BDNF expression level was increased in dextromethorphan/morphine-treated rats. Intra-VTA microinjection of (S)-WAY100135 (1 µg/rat), a selective 5-HT_1A receptor antagonist, inhibited the anti-allodynic effect of dextromethorphan/morphine. This treatment increased the cFos level in the hippocampus and the amygdala while decreased the PFC level of cFos. The hippocampal BDNF expression was significantly increased, while the amygdala and the PFC expressions of BDNF were decreased under treatment. (S)-WAY100135 plus dextromethorphan/morphine increased the hippocampal/amygdala and PFC levels of GFAP.
These findings indicate that dextromethorphan could potentiate the analgesic effect of morphine via the implication of the VTA serotonin 5-HT_1A receptors. It seems that the changes in the corticolimbic cFos/BDNF/GFAP signaling pathway may be involved in the observed anti-allodynic effect.
5-HT<inf>3</inf> receptor-mediated neural transmission of cardiorespiratory modulation by the nucleus of the tractus solitarius
2018, Serotonin: The Mediator that Spans Evolution
In the central nervous system, the nucleus of the tractus solitarius (NTS), located in the dorsal medulla, is critically involved in the control of physiological and pathological cardiorespiratory parameters as an important integrative area for both the sensory afferent signals reaching the brainstem and superior central inputs.
A large body of evidence indicates that serotonin released in the NTS from the caudal raphe group of cells plays a crucial modulatory role in the central control of blood pressure. In particular, the activation of serotonin₃ (5-HT₃) receptors induces an increase in blood pressure through direct stimulation of the ventral medullary progressive region. The activation of NTS 5-HT₃ receptors also triggers blockade of reflex cardiac responses following functional interactions with local GABA_A, NK₁, and NMDA receptors. These interactions occur in physiopathological conditions and are associated with behavioural responses to various stressful conditions that involve short- or long-term activation of the dorsomedial nucleus of the hypothalamus (DMH). In addition, blockade of NTS 5-HT₃ receptors or the use of mice lacking the 5-HT₃ receptor prevents the reduction of cyanide potassium–induced respiratory responses following low DMH stimulation, suggesting that these receptors may also participate to the long-term stress-induced bradypnea in decreasing peripheral chemoreflex responses.
Involvement of 5-HT in cardiovascular afferent modulation of brainstem circuits involved in blood pressure maintenance
2018, Serotonin: The Mediator that Spans Evolution
Stimulation of all the major cardiovascular reflexes causes the release of 5-hydroxytryptamine (5-HT) in nucleus tractus solitarii (NTS) and the nucleus ambiguus. At present the experimental evidence indicates that the major receptor subtypes involved are 5-HT₃, 5-HT_1A, 5-HT₂, and 5-HT₇. In the NTS 5-HT₃ receptor activation increases the release of glutamate from the terminals of afferent fibers. In this respect 5-HT₃ antagonists were found to attenuate the excitation of NTS neurones by these afferents and are involved in eliciting the cardiovascular changes caused by the diving response and the cardiopulmonary reflex. 5-HT₃ receptors can also activate GABAergic pathways and this action is more prominent when the agonists are given by microinjection into the NTS. Activation of 5-HT_1A receptors in the NTS can have either excitatory or inhibitory effects. Blockade of these receptors does not seem to have an influence on the excitation of NTS neurones by afferents, making their physiological role unclear. However, 5-HT_1A receptors do play a physiological role in reflex excitation of cardiac vagal preganglionic neurones located in the nucleus ambiguus. 5-HT₂ receptors, mainly 2A, are excitatory and one of their major effects is to cause sympathoexcitation. This does not apply to the sympathetic outflow to heart. Their physiological role in these pathways remains unclear. Blockade of 5-HT₇ receptors attenuates the cardiovascular changes caused by all cardiovascular reflexes tested and these receptors are involved in the excitation of NTS neurones by afferents. The lack of selective agonists for 5-HT₇ receptors makes it difficult to determine their precise physiological role. Overall it is clear that 5-HT is important for the regulation of these pathways, but the exact role and the interactions of the effects caused by activation of the different receptor subtypes remains unclear.
A hypothalamo-midbrain-medullary pathway involved in the inhibition of the respiratory chemoreflex response induced by potassium cyanide in rodents
2018, Neuropharmacology
Citation Excerpt :
Thus dlPAG activation may be at the origin of serotonin release into the NTS, to ultimately activate presynaptic 5-HT3a receptors (Hosford et al., 2014), as found previously (Bernard et al., 2008). The activation of these receptors is at the origin of vagal presynaptic glutamatergic release into the NTS (Ashworth-Preece et al., 1995), and glutamate acts on GABAergic interneurones embedded with excitatory amino acid receptors (Callera et al., 1997; Sévoz et al., 1996). In turn, GABA inhibits second-order carotid chemoreflex neurons through activation of GABAA receptors, and may block tachypneic chemoreflex responses as it was found previously for bradycardic chemoreflex responses in awake and anaesthetised rats (Sévoz et al., 1997).
Recent studies have demonstrated that a mild stimulation of the dorsomedian nucleus of the hypothalamus (DMH), a defense area, induces the inhibition of the carotid chemoreflex tachypnea. DMH activation reduces the cardiac chemoreflex response via the dorsolateral part of the periaqueductal grey matter (dlPAG) and serotonin receptors (5-HT₃ subtype) in the nucleus tractus solitarius (NTS). The objectives of this study were to assess whether dlPAG and subsequent NTS 5-HT₃ receptors are involved in chemoreflex tachypnea inhibition during mild activation of the DMH. For this purpose, peripheral chemoreflex was activated with potassium cyanide (KCN, 40 μg/rat, i.v.) during electrical and chemical minimal supra-threshold (mild) stimulation of the dlPAG or DMH. In both situations, changes in respiratory frequency (RF) following KCN administration were reduced. Moreover, pharmacological blockade of the dlPAG prevented DMH-induced KCN tachypnea inhibition. Activation of NTS 5-HT₃ receptors also reduced chemoreflex tachypnea in a dose-dependent manner. In addition, blockade of NTS 5-HT₃ receptors with granisetron (2.5 but not 1.25 mM), or the use of mice lacking the 5-HT_3a receptor (5-HT_3a KO), prevented dlPAG-induced KCN reductions in RF. A respiratory hypothalamo-midbrain-medullary pathway (HMM) therefore plays a crucial role in the inhibition of the hyperventilatory response to carotid chemoreflex.
Key role of 5-HT<inf>3</inf> receptors in the nucleus tractus solitarii in cardiovagal stress reactivity
2017, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Central 5-HT3 receptors are known to mediate an excitatory action on target cells (Kito et al., 2012). Accordingly, administration of a 5-HT3 receptor agonist into the NTS increases the local release of endogenous glutamate from vagal afferents (Ashworth-Preece et al., 1995), resulting in increased activity in second-order neurons (Jeggo et al., 2005) (Fig. 2). We have shown that stimulation of NTS 5-HT3 receptors activates a pressor efferent pathway via indirect facilitation of NO and EAA receptor-mediated mechanisms (Sévoz-Couche et al., 2002), without modifying heart rate.
Serotonin plays a modulatory role in central control of the autonomic nervous system (ANS). The nucleus tractus solitarii (NTS) in the medulla is an area of viscerosomatic integration innervated by both central and peripheral serotonergic fibers. Influences from different origins therefore trigger the release of serotonin into the NTS and exert multiple influences on the ANS. This major influence on the ANS is also mediated by activation of several receptors in the NTS. In particular, the NTS is the central zone with the highest density of serotonin₃ (5-HT₃) receptors. In this review, we present evidence that 5-HT₃ receptors in the NTS play a key role in one of the crucial homeostatic responses to acute and chronic stress: inhibitory modulation of the parasympathetic component of the ANS. The possible functional interactions of 5-HT₃ receptors with GABA_A and NK₁ receptors in the NTS are also discussed.
New insight into the therapeutic role of the serotonergic system in Parkinson's disease
2015, Progress in Neurobiology
Parkinson's disease (PD) is a common, late-onset neurodegenerative disorder that shows progressive extrapyramidal motor disorders (e.g., bradykinesia, resting tremors, muscle rigidity and postural instability) and various non-motor symptoms (e.g., cognitive impairment, mood disorders, autonomic dysfunction and sleep disorders). While dopaminergic agents such as l-3,4-dihydroxyphenylalanine (l-DOPA) and dopamine D₂ agonists are widely used for the treatment of PD, there is still high clinical unmet need for novel medications that overcome the limitations of current therapies. Evidence is now accumulating that the serotonergic nervous system is involved in the pathophysiological basis of PD and can provide benefits in the treatment of PD through its diverse functions. Among 5-HT receptor subtypes, 5-HT_1A, 5-HT₂, 5-HT₃ and 5-HT₆ receptors play an important role in modulating extrapyramidal motor disorders. In addition, 5-HT_1A, 5-HT₂, 5-HT₃, 5-HT₄ and 5-HT₆ receptors are implicated in modulation of cognitive impairment, mood disorders (e.g., depression and anxiety) and/or psychosis, which are frequently observed in patients with PD. Specifically, stimulation of 5-HT_1A receptors seems to be effective for multiple PD symptoms including parkinsonism, l-DOPA-induced dyskinesia, cognitive impairment, mood disorders and neurodegeneration of dopamine neurons. Blockade of 5-HT₂ receptors is also likely to improve parkinsonism, depressive mood and cognitive impairment. In addition, it was recently demonstrated that 5-HT_2A inverse agonists can alleviate PD psychosis. All these findings emphasize the therapeutic roles of the serotonergic system in PD and stimulate new insight into novel treatments by modulating 5-HT_1A and 5-HT₂ receptors.

View all citing articles on Scopus

View full text

5-Hydroxytryptamine3 receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius

Abstract

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Neurosci. Lett.

Neuroscience

Neuroscience

Neurosci. Lett.

Brain Res.

Trends Neurosci.

Eur. J. Pharmacol.

Neuroscience

Electrical stimulation of the vagus increases extracellular glutamate recovered from the nucleus tractus solitarii of the cat by in vivo microdialysis

Exp. Physiol.

5-Hydroxytryptamine₃ receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius