Contribution of 5-HT<sub>2</sub>Receptor Subtypes to Sleep–Wakefulness and Respiratory Control, and Functional Adaptations in Knock-Out Mice Lacking 5-HT<sub>2A</sub>Receptors

Popa, Daniela; Léna, Clément; Fabre, Véronique; Prenat, Caroline; Gingrich, Jay A.; Escourrou, P.; Hamon, Michel; Adrien, Joëlle

doi:10.1523/jneurosci.1724-05.2005

Cited by 162 publications

(110 citation statements)

References 51 publications

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“…Moreover, in an earlier study, administration of another 5-HT 2B receptorselective antagonist (ie, SB-215505) was shown to increase wakefulness at the expense of NREM and REM sleep in rats (Kantor et al, 2004), and in another study it was concluded that 5-HT exerts a 5-HT 2B receptor-mediated facilitation of NREM sleep (Popa et al, 2005), in accordance with our findings in Htr 2B − / − mice. Thus, based on these observations, we propose that the schizophrenic-like phenotype of Htr 2B − / − mice results from a combination of both the direct absence of 5-HT 2B receptor signaling and the neural adaptations triggered by the permanent lack of this receptor.…”

Section: Per Group) In the Latent Inhibition (Li) Paradigm (E) LI Wsupporting

confidence: 91%

“…Polygraphic recordings were scored visually every 15 s epoch as wakefulness, nonrapid eye movement (NREM) sleep, or rapid eye movement (REM) sleep, following classical criteria (Lena et al, 2004;Tobler et al, 1997), using Somnologica. For analysis of the spontaneous sleep-wakefulness patterns, the amounts of vigilance states for each animal were calculated for every hour throughout 48 h and summed over 24 h. REM sleep latency was calculated as the time elapsing from sleep onset after the animal had been awakened to the first episode of REM sleep (Popa et al, 2005).…”

Section: Sleep/wakefulness Patternsmentioning

confidence: 99%

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Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

Pitychoutis

Belmer

Moutkine

et al. 2015

Neuropsychopharmacol

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Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a populationspecific serotonin 2B (5-HT 2B ) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT 2B mutant (Htr 2B − / − ) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT 2B receptor in the neurobiology of schizophrenia has never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT 2B receptors in mice subjected to a comprehensive series of behavioral test screenings for schizophrenic-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters of schizophrenia were affected in Htr 2B − / − mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition, Htr 2B − / − mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT 2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected schizophreniclike phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT 2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive schizophrenic-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT 2B receptors in the neurobiology of psychotic disorders.

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Section: Per Group) In the Latent Inhibition (Li) Paradigm (E) LI Wsupporting

confidence: 91%

Section: Sleep/wakefulness Patternsmentioning

confidence: 99%

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

Pitychoutis

Belmer

Moutkine

et al. 2015

Neuropsychopharmacol

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“…5-HT2A receptors were upregulated throughout the period of sleep deprivation. Serotonin is known to play an important role in regulating sleep and wakefulness, and the 5-HT2A receptor is involved in modulating slow-wave sleep (50,51). In turn, higher serotonin levels result in downregulation of the 5-HT2A receptor, which is a G protein-coupled receptor.…”

Section: Discussionmentioning

confidence: 99%

The impact of sleep deprivation on hippocampal-mediated learning and memory in rats

Saygın¹,

Özgüner²,

Önder³

et al. 2017

BLL

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BACKGROUND: To examine the impact of different types of sleep deprivation on hippocampal-mediated learning and memory in rats. METHODS: Forty-eight Sprague-Dawley male rats were randomly assigned to 1 of 4 equal-size groups: (1) 12 hours of sleep per day (control). (2) total sleep deprivation (TSD), (3) rapid eye movement (REM) deprivation (RD), and (4) sleep restricted to 4 hours per day (SR). All rats were subjected to swimming training in the Morris water maze (MWM). At the end of the experiments, the rats were decapitated, and hippocampus tissue was analyzed for several neurotransmitters and receptors. RESULTS: The time spent at the target quadrant increased from 20.2 to 30.0 seconds in the control group on the third day of the experiment, whereas corresponding values increased from 20.2 to 21.8 seconds in the TSD group, 22.1 to 25.4 seconds in the RD group, and 21.2 to 32.0 sec in the SR group (p = 0.026). On the seventh day of the experiment, the values decreased to 25.0 seconds in controls, 22.5 in the RD group, and 23.6 in the SR group (p = 0.045). The TSD group demonstrated signifi cant decreases in glutamate and serotonin levels compared with the control group. There was a signifi cant increase in 5-HT2 a receptor expression in all intervention groups compared with the controls. CONCLUSIONS: Our results of glutamate levels and 5-HT2a receptor expression in the hippocampus seem to be primarily involved in sleep and memory regulation (Tab. 2, Fig. 4, Ref. 59). Text in PDF www.elis.sk.

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“…Despite this moderate-low in vitro affinity, CLZ exerts a number of its in vivo pharmacological actionsFparticularly the increase in PFC DA releaseFvia 5-HT 1A R activation Diaz-Mataix et al, 2005;Ichikawa et al, 2001;Rollema et al, 1997), an observation that may have several interpretations. Bortolozzi et al, 2010;Popa et al, 2005), the blockade of 5-HT 2A R by CLZ might alter the physiological balance between 5-HT 1A R and 5-HT 2A R, resulting in an increase of 5-HT 1A R-mediated neurotransmission. However, these results, obtained in anesthetized mice, together with a recent report on the effect of CLZ on dopamine release in the PFC of awake mice do not support this view, as CLZ reversed the effects of PCP on SCO in KO-2A mice, whereas it did not in KO-1A mice.…”

Section: Discussionmentioning

confidence: 99%

Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism

Kargieman

Riga

Artigas

et al. 2011

Neuropsychopharmacol

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The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP)Fused as a pharmacological model of schizophreniaFdisrupts prefrontal cortex (PFC) activity. PCP markedly increased the discharge rate of pyramidal neurons and reduced slow cortical oscillations (SCO; 0.15-4 Hz) in rat PFC. Both effects were reversed by classical (haloperidol) and atypical (clozapine) antipsychotic drugs. Here we extended these observations to mice brain and examined the potential involvement of 5-HT 2A and 5-HT 1A receptors (5-HT 2A R and 5-HT 1A R, respectively) in the reversal by clozapine of PCP actions. Clozapine shows high in vitro affinity for 5-HT 2A R and behaves as partial agonist in vivo at 5-HT 1A R. We used wild-type (WT) mice and 5-HT 1A R and 5-HT 2A R knockout mice of the same background (C57BL/6) (KO-1A and KO-2A, respectively). Local field potentials (LFPs) were recorded in the PFC of WT, KO-1A, and KO-2A mice. PCP (10 mg/kg, intraperitoneally) reduced SCO equally in WT, KO-2A, and KO-1A mice (58 ± 4%, 42 ± 7%, and 63 ± 7% of pre-drug values, n ¼ 23, 13, 11, respectively; po0.0003). Clozapine (0.5 mg/kg, intraperitoneally) significantly reversed PCP effect in WT and KO-2A mice, but not in KO-1A mice nor in WT mice pretreated with the selective 5-HT 1A R antagonist WAY-100635.The PCP-induced disorganization of PFC activity does not appear to depend on serotonergic function. However, the lack of effect of clozapine in KO-1A mice and the prevention by WAY-100635 indicates that its therapeutic action involves 5-HT 1A R activation without the need to block 5-HT 2A R, as observed with clozapine-induced cortical dopamine release.

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Contribution of 5-HT₂Receptor Subtypes to Sleep–Wakefulness and Respiratory Control, and Functional Adaptations in Knock-Out Mice Lacking 5-HT_2AReceptors

Cited by 162 publications

References 51 publications

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

The impact of sleep deprivation on hippocampal-mediated learning and memory in rats

Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism

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Contribution of 5-HT2Receptor Subtypes to Sleep–Wakefulness and Respiratory Control, and Functional Adaptations in Knock-Out Mice Lacking 5-HT2AReceptors

Cited by 162 publications

References 51 publications

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

Mice Lacking the Serotonin Htr2B Receptor Gene Present an Antipsychotic-Sensitive Schizophrenic-Like Phenotype

The impact of sleep deprivation on hippocampal-mediated learning and memory in rats

Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism

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Contribution of 5-HT₂Receptor Subtypes to Sleep–Wakefulness and Respiratory Control, and Functional Adaptations in Knock-Out Mice Lacking 5-HT_2AReceptors