Involvement of serotonin 5-HT3 receptors in the modulation of noradrenergic transmission by serotonin reuptake inhibitors: a microdialysis study in rat brain

Fernández‐Pastor, Begoña; Ortega, Jorge E.; Meana, J. Javier

doi:10.1007/s00213-013-3112-y

Cited by 13 publications

(5 citation statements)

References 86 publications

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“…Parallel to these experimental results, vortioxetine treatment has been shown to increase noradrenaline levels in the locus coeruleus and dopamine levels in the prefrontal cortex [ 8 ]. In fact, these increases have been associated with the 5HT 3 receptor antagonistic [ 9 ] and 5-HT 1A agonistic effects of this drug [ 10 ]. Indeed, in a study by Micov et al, the antiallodynic activity of vortioxetine in a model of oxaliplatin-induced neuropathy was associated with increased amounts of noradrenaline (along with serotonin) in the brainstem of mice [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…It acts as an inhibitor on the serotonin transporter, and also as an agonist (5-HT 1A ), partial agonist (5-HT 1B ) and antagonist (5-HT 1D , 5-HT 3 , 5-HT 7 ) of serotonin receptor subtypes [ 3 , 4 ]. Vortioxetine exerts its pharmacological effects in the central nervous system by regulating the release of various neurotransmitters such as noradrenaline, dopamine, histamine, acetylcholine, glutamate, gamma-aminobutyric acid, as well as serotonin [ 5 , 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

et al. 2023

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The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall–Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

et al. 2023

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“…) despite their pronounced effects on enhancing forebrain monoamine availability (Owen and Whitton ; Fernandez‐Pastor et al . ; Kaminska et al . ; Ortega et al .…”

Section: Discussionmentioning

confidence: 99%

“…The lack of effect of SSRIs on acetylcholine efflux is of interest as these agents show limited effects in treating cognitive symptoms in major depression (Jeon et al 2014;Keefe et al 2014) despite their pronounced effects on enhancing forebrain monoamine availability (Owen and Whitton 2006;Fernandez-Pastor et al 2013;Kaminska et al 2013;Ortega et al 2013). Clearly, enhancing forebrain monoamine function alone by SSRIs appears to be insufficient to broadly improve cognitive dysfunction in major depression.…”

Section: Discussionmentioning

confidence: 99%

Effects of lisdexamfetamine alone and in combination with s‐citalopram on acetylcholine and histamine efflux in the rat pre‐frontal cortex and ventral hippocampus

Hutson

Heins

Folgering

2015

Journal of Neurochemistry

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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant proportion of ADHD patients are also co-morbid for other psychiatric problems including mood disorders and these patients may be managed with a combination of psychostimulants and anti-depressants. While it is generally accepted that enhanced catecholamine signalling via the action of psychostimulants is likely responsible for the cognitive improvement in ADHD, other neurotransmitters including acetylcholine and histamine may be involved. In the present study, we have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro-drug that is approved for the treatment of ADHD on acetylcholine and histamine efflux in pre-frontal cortex and hippocampus alone and in combination with the anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an effect that was not significantly altered by co-administration of s-citalopram. Cortical and hippocampal histamine were markedly increased by LDX, an effect that was attenuated in the hippocampus but not in pre-frontal cortex when co-administered with s-citalopram. Taken together, these results suggest that efflux of acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially influenced by the co-administration of s-citalopram. Attention deficit hyperactivity disorder (ADHD) is characterized by poor attention, impulse control and hyperactivity. Some ADHD patients are also co-morbid for mood disorders and may be managed with psychostimulants (e.g. lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased the efflux of acetylcholine and histamine, neurotransmitters involved in cognitive function, which were differentially influenced when co-administered with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially affected by the co-administration of s-citalopram.

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“…Furthermore, an acute dose of vortioxetine increased norepinephrine in the nucleus locus coeruleus ( 14 ). It was suggested that this increase was not due to a direct effect of vortioxetine but via 5HT 3 receptor antagonism ( 15 ). Vortioxetine has also been demonstrated to raise dopamine levels in the prefrontal cortex ( 14 ), which is thought to be owing to a 5-HT 1A agonist effect ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of vortioxetine on pain threshold by hot-plate test in mice

İnaltekin¹,

Kıvrak²

2021

Archives of Neuropsychiatry

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Introduction: Vortioxetine is an antidepressant that has a multimadal action mechanism and has recently come into use. The present study was planned to determine whether vortioxetine affects pain threshold in mice. Method: The experimental animals were divided into four groups with 10 mice in each group. The distilled water was given to the control group, 5 mg/kg of vortioxetine was intraperitoneally administered to the first group, 10 mg/kg of vortioxetine was intraperitoneally administered to the second group and 20 mg/kg of vortioxetine was intraperitoneally administered to the third group. Mice were placed on a hot-plate at 30 and 90 minutes. Hind paw licking and jumping times of the mice on the hot plate surface (55°C) were recorded.. Results: With increasing dose (0 mg p>0.05, 5 mg p<0.001, 10 mg p<0.001, 20 mg p<0.001) and increasing time (30th minute p<0.01, 90th minute p<0.01), it was observed that the reaction time per minute, which was a reflection of pain treshold was decreased. Conclusion: The results of this study shows that vortioxetine may have a decreasing effect on pain threshold in mice. Further studies are needed to determine the mechanism by which vortioxetine exerts its hyperalgesic effect.

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Involvement of serotonin 5-HT3 receptors in the modulation of noradrenergic transmission by serotonin reuptake inhibitors: a microdialysis study in rat brain

Cited by 13 publications

References 86 publications

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

Effects of lisdexamfetamine alone and in combination with s‐citalopram on acetylcholine and histamine efflux in the rat pre‐frontal cortex and ventral hippocampus

Evaluation of the effect of vortioxetine on pain threshold by hot-plate test in mice

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