title: Serotonergic modulation of the trigeminocardiac reflex neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
abstract: Stimulation of the trigeminal nerve evokes a dramatic decrease in heart rate and blood pressure, and this reflex has generally been termed the trigeminocardiac reflex. A subset of the trigeminocardiac reflex is the diving reflex in which the nasal mucosa is stimulated with water or air-borne chemical irritants. Activation of the diving reflex evokes a pronounced bradycardia, mediated by increased parasympathetic cardiac activity, and is the most powerful autonomic reflex. However, exaggeration of this protective response could be detrimental and has been implicated in Sudden Infant Death Syndrome (SIDS). Despite the importance and strength of the trigeminocardiac reflex, there is little information about the cellular mechanisms and brain stem pathways that constitute this reflex. To address these issues, stimulation of trigeminal afferent fibers and the evoked excitatory postsynaptic currents were recorded in cardiac vagal neurons (CVNs) in an in vitro brain stem slice preparation. This synaptic pathway is robust and activation of the trigeminal pathway often evoked action potentials in CVNs. Application of the serotonin (5-HT) reuptake inhibitor citalopram significantly enhanced these responses. Consistent with the hypothesis this pathway is endogenously modulated by 5-HT receptors the 5-HT1A receptor antagonist, WAY 100635 inhibited, whereas the 5-HT2A/C receptor antagonist, ketanserin facilitated the excitatory neurotransmission to CVNs. The 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide increased, whereas the 5-HT2 receptor agonist, alpha-methylserotonin maleate salt inhibited this reflex pathway. These results indicate stimulation of trigeminal fibers evokes a powerful excitatory and polysynaptic pathway to CVNs, and this pathway is endogenously modulated and differentially enhanced and depressed, by 5-HT1A and 5-HT2 receptors, respectively.
authors: Department of Pharmacology and Physiology, George Washington University, 2300 Eye St. NW, Washington, DC 20037, USA.
authors: C
authors: C
authors: Gorini
authors: H S
authors: HS
authors: Jameson
authors: D
authors: D
authors: Mendelowitz
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015283:Citalopram / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000294:innervation*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015283:Citalopram; D004151:Dipeptides; D018691:Excitatory Amino Acid Antagonists; D007650:Ketanserin; D010879:Piperazines; D011725:Pyridines; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014633:Valine; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C042390:alpha-methylserotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C056639:2-amino-5-phosphopentanoic acid