Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia

Devroye, Céline; Cathala, Adeline; Haddjeri, Nasser; Rovera, Renaud; Vallée, Monique; Drago, Filippo; Piazza, Pier Vincenzo; Spampinato, Umberto

doi:10.1016/j.neuropharm.2016.05.024

Cited by 21 publications

(30 citation statements)

References 48 publications

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“…Indeed, 5-HT 2B R blockade reverses the cognitive deficit induced by phencyclidine (PCP) in the novel object recognition test and suppresses PCP-induced hyperlocomotion, two behavioral models classically used to predict the ability of antipsychotic drugs (APDs) to alleviate cognitive and positive symptoms of schizophrenia, respectively (Newman-Tancredi and Kleven, 2011;Porsolt et al, 2010). In keeping with the classical hypothesis that the cognitive and positive symptoms of schizophrenia result from a DA hypoactivity in the medial prefrontal cortex (mPFC) and a DA hyperactivity in the nucleus accumbens (NAc), respectively (Creese et al, 1976;Newman-Tancredi and Kleven, 2011;Svensson, 2000), the efficacy of 5-HT 2B R antagonists in these behavioral trials has been related to their ability to increase DA outflow in the mPFC and decrease it in the NAc (Auclair et al, 2010;Devroye et al, 2016).…”

Section: Introductionmentioning

confidence: 77%

“…The central serotonin 2B receptor (5-HT 2B R) is now well-established as a modulator of dopamine (DA) neuron function in the mammalian brain (Auclair et al, 2010;Devroye et al, 2015;Doly et al, 2008Doly et al, , 2009. Interestingly, recent findings have pointed out this receptor as a new pharmacological target for treating schizophrenia (Devroye et al, 2016). Indeed, 5-HT 2B R blockade reverses the cognitive deficit induced by phencyclidine (PCP) in the novel object recognition test and suppresses PCP-induced hyperlocomotion, two behavioral models classically used to predict the ability of antipsychotic drugs (APDs) to alleviate cognitive and positive symptoms of schizophrenia, respectively (Newman-Tancredi and Kleven, 2011;Porsolt et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

et al. 2017

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Recent studies have shown that serotonin receptor (5-HTR) antagonists exert opposite facilitatory and inhibitory effects on dopamine (DA) release in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), respectively, thereby leading to the proposal that these compounds could provide an interesting pharmacological tool for treating schizophrenia. Although the mechanisms underlying these effects remain unknown, several data in the literature suggest that 5-HTRs located into the mPFC could participate in this interaction. The present study, using in vivo microdialysis and electrophysiological recordings in rats, assessed this hypothesis by means of two selective 5-HTR (WAY 100635) and 5-HTR (RS 127445) antagonists. WAY 100635, administered either subcutaneously (0.16 mg/kg, s.c) or locally into the mPFC (0.1 μM), blocked the changes of mPFC and NAc DA release induced by the intraperitoneal administration of RS 127445 (0.16 mg/kg, i.p.). The administration of RS 127445 (0.16 mg/kg, i.p.) increased both dorsal raphe nucleus (DRN) 5-HT neuron firing rate and 5-HT outflow in the mPFC. Likewise, mPFC 5-HT outflow was increased following the intra-DRN injection of RS 127445 (0.032 μg/0.2 μl). Finally, intra-DRN injection of RS 127445 increased and decreased DA outflow in the mPFC and the NAc, respectively, these effects being reversed by the intra-mPFC perfusion of WAY 100635. These results demonstrate the existence of a functional interplay between mPFC 5-HTRs and DRN 5-HTRs in the control of the DA mesocorticolimbic system, and highlight the clinical interest of this interaction, as both receptors represent an important pharmacological target for the treatment of schizophrenia.

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

et al. 2017

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“…Cariprazine also binds to other receptors in vitro with moderate‐to‐low affinities; namely, the histamine H 1 , 5‐HT 2C , and α 1A ‐adrenergic receptors . Of note, both 5‐HT 1A and 5‐HT 2B receptors have been proposed to play role in the antipsychotic‐like response in animal models . The efficacy and safety of cariprazine in patients with schizophrenia have been supported by 3 positive, randomized, placebo‐controlled, phase II/III clinical studies .…”

Section: Introductionmentioning

confidence: 99%

The novel atypical antipsychotic cariprazine demonstrates dopamine D₂ receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity

et al. 2018

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AimCariprazine, a dopamine D3‐preferring D3/D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc).MethodsExtracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907.ResultsAcute oral treatment with cariprazine significantly increased and chronic cariprazine significantly decreased the number of spontaneously firing dopaminergic neurons in the VTA, but not in the SNc. Intravenous administration of cariprazine partially but significantly inhibited dopaminergic neuronal firing in both regions, which was prevented by L741,626 but not SB 277011A. In both VTA and SNc, cariprazine, SB 277011A, and L741,626 significantly antagonized the suppression of dopamine cell firing elicited by PD 128,907.ConclusionsCariprazine significantly modulates the number of spontaneously active VTA dopamine neurons and moderately suppresses midbrain dopamine neuronal activity. The contribution of dopamine D2 receptors to cariprazine's in vivo effects is prevalent and that of D3 receptors is less apparent.

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“…This disease has been managed by using pharmacological means including compounds that interact with monoaminergic transmission [47][48][49][50]. Recent data have suggested the putative role of hypocretin in modulation of schizophrenia [36].…”

Section: Other Psychiatric Disorders Regulated By Hypocretinsmentioning

confidence: 99%

Neurobiological Role of Hypocretin in Regulation of Psychiatric Disorders

Monteiro

Paes

et al. 2018

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Hypocretins are hypothalamic neuropeptides acting on the regulation of several physiological functions, the most important being the control of arousal. Hypocretin 1 and hypocretin 2 are derived from the same precursor and both bind to the orexin receptors. The hypocretinergic system has been a target of several studies that try to understand its function on the regulation of mood and behavior. The hypocretinergic system has a direct relationship with the pathways related to emotions and reward system, besides the interaction with the stress circuit. This article aims to analyze the relationship of hypocretins with anxiety, stress and depression, through a review of the existing literature.

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Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia

Cited by 21 publications

References 48 publications

Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

The novel atypical antipsychotic cariprazine demonstrates dopamine D₂ receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity

Neurobiological Role of Hypocretin in Regulation of Psychiatric Disorders

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Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia

Cited by 21 publications

References 48 publications

Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

The novel atypical antipsychotic cariprazine demonstrates dopamine D2 receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity

Neurobiological Role of Hypocretin in Regulation of Psychiatric Disorders

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The novel atypical antipsychotic cariprazine demonstrates dopamine D₂ receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity