title: Activation of 5-HT(1A) receptors attenuates tachycardia induced by restraint stress in rats.
abstract: To better understand the central mechanisms that mediate increases in heart rate (HR) during psychological stress, we examined the effects of systemic and intramedullary (raphe region) administration of the serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on cardiac changes elicited by restraint in hooded Wistar rats with preimplanted ECG telemetric transmitters. 8-OH-DPAT reduced basal HR from 356 +/- 12 to 284 +/- 12 beats/min, predominantly via a nonadrenergic, noncholinergic mechanism. Restraint stress caused tachycardia (an initial transient increase from 318 +/- 3 to 492 +/- 21 beats/min with a sustained component of 379 +/- 12 beats/min). beta-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 microg/kg) abolished the initial transient increase, indicating that sympathetic activation and vagal withdrawal were responsible for the tachycardia. Systemic administration of 8-OH-DPAT (10, 30, and 100 microg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT(1A) antagonist WAY-100635 (100 microg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 microg/kg) attenuated the sympathetically mediated sustained component (from +85 +/- 19 to +32 +/- 9 beats/min) and the vagally mediated transient (from +62 +/- 5 to +25 +/- 3 beats/min). Activation of 5-HT(1A) receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked the antitachycardic effect of the systemically administered drug but did not affect basal HR. We conclude that tachycardia induced by restraint stress is due to a sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT(1A) receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area.
authors.affiliation: Neuro-Behavioural Biology Centre, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Nakron Pathom, Thailand.
authors.forename: Sukonthar
authors.initials: S
authors.lastname: Ngampramuan
authors.forename: Mathias
authors.initials: M
authors.lastname: Baumert
authors.forename: Mirza Irfan
authors.initials: MI
authors.lastname: Beig
authors.forename: Naiphinich
authors.initials: N
authors.lastname: Kotchabhakdi
authors.forename: Eugene
authors.initials: E
authors.lastname: Nalivaiko
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019832:N-Methylscopolamine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology*; D012149:Restraint, Physical; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013565:Sympatholytics / Q000494:pharmacology; D013610:Tachycardia / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D010276:Parasympatholytics; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D044282:Receptor, Serotonin, 5-HT1A; D001262:Atenolol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019832:N-Methylscopolamine