The Experts below are selected from a list of 103500 Experts worldwide ranked by ideXlab platform
Berend Olivier - One of the best experts on this subject based on the ideXlab platform.
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5 ht1b Receptor knockout mice show no adaptive changes in 5 ht1a Receptor function as measured telemetrically on body temperature and heart rate responses
Brain Research Bulletin, 2002Co-Authors: Adriaan J Bouwknecht, Berend Olivier, Theo H. Hijzen, Jan Van Der Gugten, R A A Maes, Rene HenAbstract:Abstract Two presynaptic Receptors play an important role in the regulation of serotonergic neurotransmission, i.e., the 5-HT1A and 5-HT1B Receptor. The present study focuses on putative adaptive changes in the 5-HT1A Receptor system in mice that lack 5-HT1B Receptors (5-HT1B KO). 5-HT1A Receptor Sensitivity was assessed in vivo in two models of presynaptic 5-HT1A Receptor activity: agonist-induced hypothermia and prevention of stress-induced hyperthermia. The effects of 5-HT1A Receptor activation by flesinoxan (0.1–3.0 mg/kg s.c.) were determined telemetrically on body temperature and heart rate in 5-HT1B KO and wild-type (WT) mice. Flesinoxan induced hypothermia dose-dependently without affecting heart rate and prevented stress-induced hyperthermia and tachycardia equipotently in both genotypes. Specificity of these responses was confirmed by blockade with the selective 5-HT1A Receptor antagonist WAY100635 (1.0 mg/kg s.c.). The importance of continuous sampling in freely moving subjects to improve appropriate characterization of mutants is discussed. 5-HT1B KO mice showed no shift in 5-HT1A Receptor Sensitivity compared to WT mice. This study found no indications for adaptive changes in presynaptic 5-HT1A Receptor function in 5-HT1B KO mice as measured telemetrically on body temperature and heart rate responses.
Philip J. Cowen - One of the best experts on this subject based on the ideXlab platform.
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Effect of paroxetine and nefazodone on 5-HT1A Receptor Sensitivity
Psychopharmacology, 1997Co-Authors: P. A. Sargent, D. J. Williamson, G. Pearson, J. Odontiadis, Philip J. CowenAbstract:Animal experimental studies suggest that the therapeutic effect of selective serotonin re-uptake inhibitors (SSRIs) may involve neuroadaptive changes in pre- and post-synaptic serotonin1A (5-HT1A) Receptors. We used the endocrine and hypothermic responses to the 5-HT1A Receptor agonist, gepirone (20 mg orally), to assess 5-HT1A Receptor Sensitivity in 37 healthy male volunteers who were studied before and following random double-blind, allocation to treatment with paroxetine, nefazodone or placebo for 17 days. Following antidepressant drug treatment, hypothermic responses to gepirone were markedly decreased by paroxetine but only slightly diminished by nefazodone. Paroxetine also lowered the growth hormone and cortisol responses to gepirone. There was no change in either hypothermic or endocrine response following placebo treatment. Our results suggest that paroxetine treatment produces a striking attenuation of measures of both pre- and post-synaptic 5-HT1A Receptor function. Nefazodone appears to decrease the Sensitivity of 5-HT1A autoReceptors to some extent and this effect may contribute to its antidepressant activity.
A L Sharpley - One of the best experts on this subject based on the ideXlab platform.
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effect of lofepramine on 5 ht function and sleep
Journal of Affective Disorders, 1993Co-Authors: J R E Herdman, P J Cowen, G M Campling, R A Hockney, D Laver, A L SharpleyAbstract:We studied the effect of the tricyclic antidepressant lofepramine (140-210 mg daily for 16 days) on 5-hydroxytryptamine 1A (5-HT1A) Receptor Sensitivity in healthy volunteers, using a buspirone neuroendocrine challenge paradigm (30 mg orally). We also studied the effect of lofepramine on platelet 5-HT content and sleep architecture. Lofepramine treatment did not alter the hypothermic, endocrine or amnesic effects of buspirone but significantly lowered platelet 5-HT content and decreased rapid eye movement sleep. Our findings suggest that at clinically used doses, lofepramine inhibits the uptake of 5-HT and produces changes in sleep architecture characteristic of tricyclic antidepressants. However, lofepramine does not appear to alter the Sensitivity of 5-HT1A Receptors.
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slow wave sleep and 5 ht2 Receptor Sensitivity in generalised anxiety disorder a pilot study with ritanserin
Psychopharmacology, 1992Co-Authors: J M Da Roza Davis, A L Sharpley, P J CowenAbstract:Eight patients with generalised anxiety disorder (GAD) and eight matched healthy controls had their polysomnogram measured on two occasions separated by 1 week. On one occasion they received the 5-HT2 Receptor antagonist, ritanserin (5 mg orally) and on the other matching placebo. The increase in slow wave sleep produced by ritanserin was the same in GAD patients as in healthy controls. These findings do not support the hypothesis that GAD is associated with a generalised hyperSensitivity of brain 5-HT2 Receptors; however, the present data cannot exclude the presence of a regionally specific change in this Receptor subtype in anxiety disorders.
Sergio Tufik - One of the best experts on this subject based on the ideXlab platform.
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dopamine transporter regulation during four nights of rem sleep deprivation followed by recovery an in vivo molecular imaging study in humans
Sleep, 2010Co-Authors: R C S Martins, Monica L Andersen, Silverio Garbuio, Lia Bittencourt, Camila Guindalini, Ming Chi Shih, Marcelo Queiroz Hoexter, Rodrigo A Bressan, Mario Luiz Vieira Castiglioni, Sergio TufikAbstract:CHRONIC SLEEP LOSS IS INCREASINGLY COMMON IN INDUSTRIALIZED SOCIETIES, AFFECTING ABOUT 45% OF ADULTS.1 SLEEP DEPRIVATION INDUCES behavioral, hormonal, and neurochemical alterations.2 The stress inherent in sleep deprivation causes changes in the concentration of hormones such as cortisol3 as well as in prolactin and estradiol, which are known to influence dopaminergic transmission.4 Studies have suggested that dopamine (DA) is responsible for the behavioral changes observed after sleep deprivation. Since the 1970s, Tufik and colleagues demonstrated an enhancement in DA Receptor Sensitivity after rapid eye movement (REM) sleep deprivation in rats.2,5 Specifically, REM sleep deprivation has been shown to be related to changes in D2 post-synaptic Receptor Sensitivity in the rat striatum (STR).6,7 Recently, a study using microdialysis coupled with electrophysiological recordings reported an increase in DA concentrations during wakefulness and REM sleep compared to the concentration associated with slow wave sleep (SWS) in rats.8 Profound DA depletion in mice promotes the complete suppression of REM sleep,9 and DA transporter (DAT) knockout mice exhibit increased wakefulness and less SWS.10 An autoradiographic study in REM sleep deprived rats showed an increase in DA post-synaptic Receptor Sensitivity,6 however there was no observable increase in DAT density.11 A recent imaging study in humans indicated that DA release increases after 24 hours of total sleep deprivation, as reflected by DA cell firing and/or release, rather than reduced DA reuptake.12 Although the recovery of sleep deprivation is marked by several neurochemical alterations13 and studies have suggested that REM sleep is the main modulator of the catecholaminergic system,2,5–7 the effect of longer periods of selective REM sleep deprivation on DAT availability, associated with electroencephalography, has not yet been evaluated. In addition, neuroimaging studies have not been performed in individuals subjected to both total and REM sleep deprivation, followed by sleep recovery. Therefore, we set out to assess DAT density in the human brain after 4 nights of REM sleep deprivation and 3 nights of sleep recovery using single positron emission computed tomography (SPECT) and [99mTc]TRODAT-1, a selective DAT imaging agent. The specific sleep deprivation and recovery periods were chosen based on the fact that REM sleep is concentrated in the second half of sleep. Thus, individuals who experience daily sleep deprivation as a consequence of bedtime restriction lose a considerable percentage of this stage of sleep. Frequently, this sleep debt is compensated during the weekends by obtaining extra sleep over and above the daily requirement, a scenario that was replicated in this investigation by the REM sleep-deprived group. Reproducibility of the DAT density was ensured by a control group that slept regularly and had SPECT imaging conducted at three time-points. Based on another common type of individual who spends long periods of time without sleeping as a consequence of professional or personal burden, volunteers in a third experimental group were sleep deprived for 2 consecutive nights and subjected to the same evaluations. We monitored sleep architecture and measured cortisol, prolactin, and estradiol levels during the course of entire investigation. The working hypotheses were (1) REM sleep would induce increases in dopaminergic activity after sleep deprivation and (2) selective REM sleep deprivation for a prolonged period would result in down-regulation of DAT, enhancing dopaminergic neurotransmission.
Judith R Homberg - One of the best experts on this subject based on the ideXlab platform.
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enhanced aggressive phenotype of tph2 knockout rats is associated with diminished 5 ht1a Receptor Sensitivity
Neuropharmacology, 2019Co-Authors: Deborah G A Peeters, Adrian Newmantancredi, S.f. De ,boer, Anneke Terneusen, Mark A Varney, Robbertjan Verkes, Judith R HombergAbstract:Brain serotonin (5-HT) plays a key role in aggressive behaviours and related psychopathologies, but its precise mechanism of action remains elusive. Genetic animal models may provide a tool to elucidate the relationship between aggression and serotonin. The present study showed that tryptophan hydroxylase 2 (Tph2) knockout (KO) rats, which exhibit profoundly diminished extracellular serotonin levels, display increased aggressiveness compared to their Tph2 wildtype (WT) counterparts. However, the level of aggression in Tph2 KO rats did not equal that of feral wild type Groningen (WTG) rats. To investigate whether enhanced 5-HT1A Receptor functionality may be present in Tph2 KO rats, we tested the acute anti-aggressive potency of the highly selective 5-HT1A Receptor full agonist NLX-112 (a.k.a. befiradol or F13640). Data show that compared to Tph2 WT and WTG rats, the NLX-112 dose-effect curve was shifted to the right in Tph2 KO animals. These results suggest that, unlike previous reports in Tph2 KO mice, Tph2 KO rats have a decreased 5-HT1A Receptor Sensitivity compared to both Tph2 WT and WTG animals.
