Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    Computational modelling of 5-HT receptor-mediated reorganization of the brainstem respiratory network.

    Eur J Neurosci 2011 Oct 7;34(8):1276-91. Epub 2011 Sep 7.
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
    Brainstem respiratory neurons express the glycine α(3) receptor (Glyα(3) R), which is a target of modulation by several serotonin (5-HT) receptor agonists. Application of the 5-HT(1A) receptor (5-HT(1A) R) agonist 8-OH-DPAT was shown (i) to depress cellular cAMP, leading to dephosphorylation of Glyα(3) R and augmentation of postsynaptic inhibition of neurons expressing Glyα(3) R (Manzke et al., 2010) and (ii) to hyperpolarize respiratory neurons through 5-HT-activated potassium channels. These processes counteract opioid-induced depression and restore breathing from apnoeas often accompanying pharmacotherapy of pain. The effect is postulated to rely on the enhanced Glyα(3) R-mediated inhibition of inhibitory neurons causing disinhibition of their target neurons. To evaluate this proposal and investigate the neural mechanisms involved, an established computational model of the brainstem respiratory network (Smith et al., 2007), was extended by (i) incorporating distinct subpopulations of inhibitory neurons (glycinergic and GABAergic) and their synaptic interconnections within the Bötzinger and pre-Bötzinger complexes and (ii) assigning the 5-HT(1A) R-Glyα(3) R complex to some of these inhibitory neuron types in the network. The modified model was used to simulate the effects of 8-OH-DPAT on the respiratory pattern and was able to realistically reproduce a number of experimentally observed responses, including the shift in the onset of post-inspiratory activity to inspiration and conversion of the eupnoeic three-phase rhythmic pattern into a two-phase pattern lacking the post-inspiratory phase. The model shows how 5-HT(1A) R activation can produce a disinhibition of inspiratory neurons, leading to the recovery of respiratory rhythm from opioid-induced apnoeas.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with
    Source Status
    Publisher SiteFound ListingPossible

    Similar Publications

    The potency of different serotonergic agonists in counteracting opioid evoked cardiorespiratory disturbances.
    Philos Trans R Soc Lond B Biol Sci 2009 Sep;364(1529):2611-23
    Institute of Membrane and Systems Biology, University of Leeds, , Leeds LS2 9JT, UK.
    Serotonin receptor (5-HTR) agonists that target 5-HT(4(a))R and 5-HT(1A)R can reverse mu-opioid receptor (mu-OR)-evoked respiratory depression. Here, we have tested whether such rescuing by serotonin agonists also applies to the cardiovascular system. In working heart-brainstem preparations in situ, we have recorded phrenic nerve activity, thoracic sympathetic chain activity (SCA), vascular resistance and heart rate (HR) and in conscious rats, diaphragmatic electromyogram, arterial blood pressure (BP) and HR via radio-telemetry. Read More
    The counteraction of opioid-induced ventilatory depression by the serotonin 1A-agonist 8-OH-DPAT does not antagonize antinociception in rats in situ and in vivo.
    Anesth Analg 2009 Apr;108(4):1169-76
    Clinic of Anesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
    Background: Spontaneous breathing during mechanical ventilation is gaining increasing importance during intensive care but is depressed by narcotics, such as opioids. Serotonin 1A-receptor (5-HT(1A)-R) agonists have been shown to antagonize opioid-induced ventilatory depression, but both enhancement and attenuation of nociceptive reflexes have been found with different experimental models. To clarify contradictory findings, we simultaneously determined dose-response functions of the standard 5-HT(1A)-R-agonist 8-OH-DPAT and two different opioids for spontaneous ventilation and nociception. Read More
    5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function.
    Hypertension 2007 Aug 18;50(2):368-76. Epub 2007 Jun 18.
    Department of Pharmacology and Physiology, George Washington University, 2300 Eye St, NW, Washington, DC 20037, USA.
    Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and gamma-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. Read More
    Dual effects of 5-HT(1a) receptor activation on breathing in neonatal mice.
    J Neurosci 2014 Jan;34(1):51-9
    Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, Alaska 99775, Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, Veteran's Affairs Medical Center, Iowa City, Iowa 52242, and Departments of Neurology, and Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242.
    Inhibitory 5-HT(1a) receptors are located on serotonin (5-HT) neurons (autoreceptors) as well as neurons of the respiratory network (heteroreceptors). Thus, effects on breathing of 5-HT(1a) agonists, such as (R)-(+)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), could either be due to decreased firing of 5-HT neurons or direct effects on the respiratory network. Mice in which the transcription factor LMX1B is genetically deleted selectively in Pet1-1-expressing cells (Lmx1b(f/f/p)) essentially have complete absence of central 5-HT neurons, providing a unique opportunity to separate the effect of activation of downstream 5-HT(1a) heteroreceptors from that of autoreceptors. Read More