Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli.

Segal, Menahem

doi:10.1113/jphysiol.1979.sp012628

Cited by 243 publications

(56 citation statements)

References 29 publications

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“…Patients had LHb rsFC to the DRN that have been linked to serotoninergic functions. Our results revealed a unique Hb rsFC for patients with CRPS to brainstem structures that have not been previously linked to the Hb, for example, the LC, PBN, and NCS, all of which have repeatedly been associated with pain processing and pain modulation (Leichnetz et al 1978;Segal 1979;Cechetto et al 1985). These functional connections, together with altered Hb rsFC to the rest of the brain, may contribute to spontaneous, ongoing pain in patients.…”

Section: Hb Rsfc In Patients With Crpsmentioning

confidence: 83%

Habenula functional resting-state connectivity in pediatric CRPS

Erpelding

Sava

Simons

et al. 2014

Journal of Neurophysiology

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The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10–17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

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Section: Hb Rsfc In Patients With Crpsmentioning

confidence: 83%

Habenula functional resting-state connectivity in pediatric CRPS

Erpelding

Sava

Simons

et al. 2014

Journal of Neurophysiology

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“…In addition, the LC is a strategically situated nucleus, located where the noradrenergic and the serotonergic systems establish a close functional relationship. The LC receives dense 5-HT projections coming from dorsal raphe and pericoerulear 5-HT neurons (Segal, 1979). Interestingly, it has been suggested that LC neurons are subject to the indirect influence of 5-HT 1A receptors (Szabo and Blier, 2001c).…”

mentioning

confidence: 99%

In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Role of Opioid, α₂-Adrenergic, and 5-Hydroxytryptamine_1A Receptors

Berrocoso

Micó²

2007

J Pharmacol Exp Ther

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The locus coeruleus (LC) is involved in several neural pathways responsible for some somatic and emotional processes, such as pain and depression; its activity is regulated by several receptors, such as opioid, ␣ 2 -adrenergic, and 5-hydroxytryptamine (5-HT) 1A receptors. The present study investigates the in vivo effects of venlafaxine, an antidepressant with analgesic properties, on locus coeruleus neurons, and its modulation by opioid, ␣ 2 -adrenergic, and 5-HT 1A receptors. The results show that acute administration of venlafaxine produced a dose-dependent, complete inhibition of LC activity. This inhibitory effect was not reversed by the opioid receptor antagonist naloxone, but subsequent administration of idazoxan, an ␣ 2 -adrenoceptor antagonist, did reverse it. The preadministration of the 5-HT 1A receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) (1 and 40 g/kg) significantly enhanced the venlafaxine inhibitory effect, decreasing the ED 50 by 56 and 44%, respectively. A 14-day treatment with venlafaxine (40 mg/kg/ day) induced a suppression of the firing activity of LC neurons. In these treated animals, venlafaxine produced an inhibitory effect similar to that in nontreated animals. This inhibitory effect was not reversed by naloxone, but it was reversed by idazoxan. In addition, the preadministration of 8-OH-DPAT (40 g/kg) significantly enhanced the venlafaxine effect, decreasing the ED 50 by 60%. These results suggest that the effect of venlafaxine on LC neurons is modulated by ␣ 2 -adrenergic and 5-HT 1A receptors, and not by opioid receptors. These data could contribute to the further understanding of the antidepressant and analgesic mechanism of action of venlafaxine.Venlafaxine is a dual 5-hydroxytryptamine (serotonin)/ noradrenaline (5-HT/NA) reuptake inhibitor (SNRI) antidepressant that blocks the synaptosomal uptake of 5-HT at low doses and NA at higher doses (Muth et al., 1986;Dawson et al., 1999). In addition to its antidepressant effect, venlafaxine also has analgesic properties (Saarto and Wiffen, 2005). The fact that antidepressants have antidepressant and analgesic properties suggests that monoamines, and primarily 5-HT and NA, are implicated in depression as well as in pain. These pathologies have a high comorbidity, implying a possible interrelated or common neurochemical mechanism and/or neuroanatomical substrate.

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“…It is well established that locus coeruleus (LC) NE neurons modulate the 5-HT system, and evidence is accumulating for a major influence of 5-HT on the NE system (see Haddjeri et al, 1997;Kaehler et al, 1999). The LC receives dense 5-HT projections coming from dorsal raphe and pericoerulear 5-HT neurons (Aston-Jones et al, 1991;Kaehler et al, 1999), which exert an inhibitory role (Léger and Descarries, 1978;Segal, 1979). This is supported by the observation that lesioning 5-HT neurons with a 5-HT neurotoxin produced a marked elevation of firing rate of NE neurons (Haddjeri et al, 1997).…”

mentioning

confidence: 99%

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

Szabo¹,

Blier²

2002

J Pharmacol Exp Ther

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YM992 [(S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride] is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and a potent 5-HT 2A antagonist. The aim of the present study was to assess, using in vivo extracellular unitary recordings, the effect of acute and sustained administration of YM992 (40 mg kg Ϫ1 day Ϫ1 s.c., using osmotic minipumps) on the spontaneous firing activity of locus coeruleus (LC) norepinephrine (NE) neurons. Acute intravenous injection of YM992 (4 mg kg Ϫ1 ) significantly decreased NE neuron firing activity by 29% and blocked the inhibitory effect of a subsequent injection of the 5-HT 2 agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride]. A 2-day treatment with YM992 decreased the firing rate of NE neurons by 66%, whereas a partial recovery was observed after a 7-day treatment and a complete one after a 21-day treatment. Following the injection of the ␣ 2 -adrenoceptor antagonist idazoxan (1 mg kg -1 i.v.), NE neuron firing was equalized in controls and 2-day YM992-treated rats. This put into evidence an increased degree of activation of ␣ 2 -adrenergic autoreceptors in the treated rats. The suppressant effect of the ␣ 2 -adrenoceptor agonist clonidine was significantly decreased in longterm YM992-treated rats. The recovery of LC firing activity after long-term YM992 administration could thus be explained by a decreased sensitivity of ␣ 2 -adrenergic autoreceptors. Sustained SSRI administration leads to a gradual reduction of the firing activity of NE neurons during long-term administration, whereas YM992 produced opposite effects. The exact basis for the increased synaptic availability of NE by YM992 remains to be elucidated. This NE activity, resulting from 5-HT reuptake inhibition plus 5-HT 2A receptor antagonism, might confer additional benefits in affective and anxiety disorders.The norepinephrine (NE) and the serotonin (5-hydroxytryptamine; 5-HT) systems have both been implicated in anxiety and affective disorders. Although the etiopathology of these two disorders remains enigmatic, greater knowledge exists pertaining to the interactions/alterations of these monoaminergic systems during antidepressant drug treatment. It is well established that locus coeruleus (LC) NE neurons modulate the 5-HT system, and evidence is accumulating for a major influence of 5-HT on the NE system (see Haddjeri et al., 1997;Kaehler et al., 1999). The LC receives dense 5-HT projections coming from dorsal raphe and pericoerulear 5-HT neurons (Aston-Jones et al., 1991;Kaehler et al., 1999), which exert an inhibitory role (Léger and Descarries, 1978;Segal, 1979). This is supported by the observation that lesioning 5-HT neurons with a 5-HT neurotoxin produced a marked elevation of firing rate of NE neurons (Haddjeri et al., 1997). Long-term, but not acute or short-term (2-day) administration of SSRIs decreases the spontaneous firing activity of LC NE neurons in the rat (Béïque et al.,1998;Szabo et al., 2000;Szabo and Blier, 2001a;Grant a...

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Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli.

Cited by 243 publications

References 29 publications

Habenula functional resting-state connectivity in pediatric CRPS

Habenula functional resting-state connectivity in pediatric CRPS

In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Role of Opioid, α₂-Adrenergic, and 5-Hydroxytryptamine_1A Receptors

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

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Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli.

Cited by 243 publications

References 29 publications

Habenula functional resting-state connectivity in pediatric CRPS

Habenula functional resting-state connectivity in pediatric CRPS

In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Role of Opioid, α2-Adrenergic, and 5-Hydroxytryptamine1A Receptors

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

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Product

Resources

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In Vivo Effect of Venlafaxine on Locus Coeruleus Neurons: Role of Opioid, α₂-Adrenergic, and 5-Hydroxytryptamine_1A Receptors

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons