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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/R132    most recent 00464.2007v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ngampramuan, S. Articles by Nalivaiko, E. PubMed PubMed Citation Articles by Ngampramuan, S. Articles by Nalivaiko, E.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Activation of 5-HT_1A receptors attenuates tachycardia induced by restraint stress in rats

¹Neuro-Behavioural Biology Centre, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Nakron Pathom, Thailand; ²Centre for Biomedical Engineering, School of Electrical and Electronic Engineering, University of Adelaide, and ³Department of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, Australia

Submitted 29 June 2007 ; accepted in final form 19 October 2007

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). β-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 µg/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 µg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT_1A antagonist WAY-100635 (100 µg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 µg/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.

serotonin; psychological stress; heart rate; sympathetic; medullary raphe