In vivo modulation of vagal-identified dorsal medullary neurones by activation of different 5-Hydroxytryptamine 2 receptors in rats (original) (raw)
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Neuropharmacology, 2000
In in vivo experiments, 5-hydroxytryptamine (5-HT) and (±)-2,5-dimethoxy-4-iodoamphetamine HCl (DOI), a 5-HT 2 receptor agonist, were applied by ionophoresis to rat nucleus tractus solitarius (NTS) neurones identified by their vagal and cardiopulmonary afferent inputs to test whether the response of NTS cells to 5-HT 2 receptor activation was related to whether they received monoor polysynaptic vagal inputs and their presumed function as defined by their afferent input. Cells were classified on the basis of the variability of the latency of the vagal-evoked spikes: this varied by less than 3 ms for Group 1, from 3 to 5 ms for Group 2, and more than 5 ms for Group 3. Both 5-HT and DOI inhibited most Group 1 cells (16/18) and inactive (without ongoing activity) cells (8/13) in Group 2. Cells inhibited by DOI were also inhibited by cardiopulmonary afferent stimulation, evoked by atrial phenylbiguanide administration. By contrast, application of 5-HT and DOI excited the majority of Group 3 cells (14/19) and Group 2 with ongoing activity (7/9). Cells excited by DOI were also activated by cardiopulmonary stimulation. Both actions of DOI were reversed by application of ketanserin (n=15). In conclusion, these data demonstrate that activation of 5-HT 2 receptors in the NTS produces different effects dependent on whether the neurones received mono-or polysynaptic vagal input and their response to cardiopulmonary afferent stimulation.
British Journal of Pharmacology, 1992
The actions of 5-hydroxytryptamine (5-HT) and some 5-HTA receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2 In the presence of tetrodotoxin (1 tiM) to block any indirect effects, bath application of 5-HT (0.3-30 AM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3 The 5-HTA receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT, receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50s were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 ptM and buspirone 110 nM. 5 At a concentration of 3 SAM, the putative 5-HTIA receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8-azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17. 6 The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 jiM) and the 5HT3 receptor antagonist, tropisetron (3 tiM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization. 7 It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.
British Journal of Pharmacology, 2003
1 Systemic administration of phenethylamine-derived, 5-hydroxytryptamine 2 (5-HT 2 ) receptor agonists inhibits the firing of midbrain 5-HT neurones, but the 5-HT receptors involved are poorly defined, and the contribution of peripheral mechanisms is uncertain. This study addresses these issues using extracellular recordings of 5-HT neurones in the dorsal raphe nucleus of anaesthetised rats. 2 The 5-HT 2 receptor agonists DOI ((7)-2,5-dimethoxy-4-iodoamphetamine hydrochloride) and DOB ((7)-2,5-dimethoxy-4-bromoamphetamine hydrobromide), caused a dose-related (10 -100 mg kg À1 i.v.) inhibition of 5-HT neuronal activity, with the highest dose reducing firing rates by 480%.
British Journal of Pharmacology, 1990
1 5-Hydroxytryptamine (5-HT) was applied by microiontophoresis in the vicinity of identified sympathetic preganglionic neurones in the upper thoracic spinal cord of the rat, in vivo. 2 Sympathetic preganglionic neurones responded in one of three ways to 5-HT: by (a) excitation (76%), (b) inhibition (4%) or (c) in a biphasic manner (5%). 3 The excitatory responses evoked by 5-HT were mimicked by 5-carboxamidotryptamine (5-CT) and a-methyl-5-hydroxytryptamine (a-Me-5-HT). The inhibitory and biphasic responses evoked by 5-HT were mimicked by 2-methyl-5-hydroxytryptamine (2-Me-5-HT). The observed responses evoked by 5-HT and selective agonists may be different on the same cell. In several instances a single neurone excited by one agonist was inhibited by another agonist. 4 The 5-HT2-receptor antagonists, ketanserin and LY 53857, failed to abolish selectively the excitatory responses evoked by 5-HT and a-Me-5-HT, when applied by microiontophoresis. The antagonists nonselectively reduced the excitatory responses evoked by 5-HT, 5-CT, a-Me-5-HT, D,L-homocysteic acid (DLH) and noradrenaline (NA). A reduction in synaptically evoked activity was also observed. 5 The 5-HT3-receptor antagonist, ICS 205-930, failed to abolish the inhibitory responses evoked by 5-HT.
Hypoglossal nerve response to 5-HT3 drugs injected into the XII nucleus, and vena cava in the rat
Sleep
Systemically administered ondansetron, a 5-HT3 receptor antagonist, reduces obstructive sleep-disordered breathing (OSDB) events in the English bulldog. The neural mechanisms through which ondansetron acts are unknown. 5-HT3 receptor immunoreactivity and mRNA have been detected in the vicinity of upper airway dilator motoneurons (UAWDMn's), suggesting that this receptor may contribute to the state-dependent modulation of UADMn's. To characterize 5-HT3 receptor activity within a representative UAWD nucleus, we performed acute microinjections of selective 5-HT3 drugs, 1-(m-Chlorophenyl)-biguanide HCl, an agonist, and ondansetron, an antagonist, into a major population of UADMn's, the hypoglossal nucleus (XII), in anesthetized, paralyzed and mechanically-ventilated rats. The 5-HT3-selective drugs neither altered the baseline XII nerve activity nor the excitatory effect of 5-HT microinjected into the XII. In contrast, systemic-administration of ondansetron (3 mg/kg) produced...
Brain Research, 1992
Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT. 100 p.M) and the selective 5-HT~ receptor agonist 2-methyl-5-HT (2-CH ~-5-HT, 100 p.M) depolarized 86% of NTS neurons at resting membrane potential (V m). This response was resistant to tetrodotoxin (TTX) and (~o-+ application. In addition, 2-CH3-5-HT (500 nM-10() p.M) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant. but was abolished by Co-'+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bieuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH.r5-HT between 500 nM and l p.M decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT 3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10/zM) reversibly blocked the effects of 2-CH.r5-HT at all doses examined, it is concluded that 5-HT.x receptors can mediate both pre-and postsynaptic responses in the NTS.
Neuroscience, 2007
Serotonin (5-HT), and in particular 5-HT 2 receptors, play an important role in cardiorespiratory function within the brainstem. In addition, abnormalities in the 5-HT system have been implicated in many cardiorespiratory disorders, including sudden infant death syndrome. However little is known about the mechanisms of action of 5-HT 2 receptors in altering the activity of parasympathetic cardiac neurons in the brainstem. In this study we examined the effects of activation of different subtypes of 5-HT 2 receptors on spontaneous and respiratory evoked GABAergic neurotransmission to cardioinhibitory vagal neurons within the nucleus ambiguus as well as rhythmic fictive inspiratoryrelated activity. A single application of α-Me-5-hydroxytryptamine maleate (α-Me-5-HT), a 5-HT 2 receptor agonist, did not significantly alter the frequency of spontaneous or respiratory-evoked GABAergic inhibitory post-synaptic currents (IPSCs) in cardiac vagal neurons. However, repetitive successive applications of α-Me-5-HT elicited a long-lasting (≥ 1 hour) decrease in the frequency of spontaneous as well as inspiratory-related GABAergic IPSCs to cardiac vagal neurons. This study demonstrates multiple, but not single applications of the 5-HT 2 receptor agonist α-Me-5-HT caused a long-lasting inhibition of both spontaneous and fictive inspiratory-related GABAergic neurotransmission to CVNs which can be prevented by the 5-HT 2B receptor antagonist SB204741, but persisted with the 5-HT 2A/2C receptor antagonist ketanserin. The 5-HT 2 receptor agonist α-Me-5-HT also reversibly and transiently excited central fictive inspiratory activity which was abolished by ketanserin, but was unaffected by the 5-HT 2B receptor antagonist SB204741.
Neuropharmacology, 1997
The aim of the present study was to characterize in vivo the 5-HT receptor subtypes which mediate the effect of microiontophoretic applied 5-HT in the guinea pig head of caudate nucleus and orbitofrontal cortex. 5-HT and the preferential 5-HT2A receptor agonist DOI and the preferential 5-HT2C receptor agonist mCPP, suppressed the quisqualate (QUIS)-induced activation of neurons in both structures. The inhibitory effect of DOI and mCPP was not prevented by acute intravenous administration of the 5-HT12 receptor antagonist metergoline (2 mg/kg) and the 5-HT2A/2C receptor antagonist ritanserin (2 mg/kg) in the two regions nor by the selective 5-HT2A receptor antagonist MDL100907 (1 mg/kg) in the head of caudate nucleus. However, the inhibitory effect of DOI, but not that of mCPP, was antagonized by a 4-day treatment with metergoline and ritanserin (2 mg/kg/day; using minipumps implanted subcutaneously) in head of caudate nucleus, but not in orbitofrontal cortex. Microiontophoretic ejection of the 5-HT1A/7 receptor agonist 8-OH-DPAT and of the -HT1A receptor antagonist WAY100635 both suppressed the spontaneous and QUIS-activated firing activity of orbitofrontal cortex neurons. At currents which did not affect the basal discharge activity of the neuron recorded, microiontophoretic application of WAY100635 and BMY7378 failed to prevent the inhibitory effect of 8-OH-DPAT. The inhibitory effect of gepirone, which is a -HT1A receptor agonist but devoid of affinity for 5-HT7 receptors, was also not antagonized by WAY100635. Altogether, these results suggest the presence of atypical 5-HT1A receptors in the orbitofrontal cortex. The present results also indicate that the suppressant effect of DOI may be mediated by 5-HT2A receptors in head of caudate nucleus and atypical 5-HT2 receptors in orbitofrontal cortex. © 1997 Elsevier Science Ltd.
British Journal of Pharmacology, 1993
1 The biophysical and pharmacological properties of 5-hydroxytryptamine (5-HT)-evoked currents in rabbit nodose ganglion neurones in culture have been determined by use of the whole-cell and outside-out membrane patch recording modes of the patch-clamp technique. 2 In 49% of cells investigated the bath application of 10-5 M 5-HT at negative holding potentials elicited an inward current. The whole-cell response to 5-HT reversed in sign (E5-HT) at approximately -2 mV and exhibited inward rectification.