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.
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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
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
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
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