Submitted on June 29, 2007
Accepted on October 19, 2007
ACTIVATION OF 5-HT1A RECEPTORS ATTENUATES TACHYCARDIA INDUCED BY RESTRAINT STRESS IN RATS
Sukonthar Ngampramuan1, Mathias Baumert2, Mirza Irfan Beig3, Naiphinich Kotchabhakdi1, and Eugene Nalivaiko4*
1 Neuro-behavioural biology centre, Mahidol University, Salaya, Thailand
2 School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, South Australia, Australia
3 Human Physiology, Flinders University, Adelaide, South Australia, Australia
4 Human Physiology, Flinders University, Bedford Park, Australia
* To whom correspondence should be addressed. E-mail: eugene.nalivaiko{at}flinders.edu.au.
In order to better understand central mechanisms that mediate increase in the heart rate during psychological stress, we examined effects of systemic and intra-medullary (raphe region) administration of 5-HT1A-receptor agonist 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)-tetraline] on cardiac changes elicited by restraint in Hooded Wistar rats with pre-implanted ECG telemetric transmitters. 8-OH-DPAT reduced basal heart rate from 356 ± 12 to 284 ± 12 BPM, predominantly via non-adrenergic, non-cholinergic mechanisms. Restraint stress caused tachycardia (initial transient from 318±3 to 492±21 BPM and a sustained component of 379±12 BPM). 
-adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methyl-scopolamine abolished the initial transient, 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; this effect was suppressed by 5-HT1A antagonist WAY-100,635 (100 µg/kg). Given alone, the antagonist was without effect. Systemically injected 8-OH-DPAT (100 µg/kg) attenuated both the sympathetically-mediated sustained component (from +85±19 to +32±9 BPM) and the vagally-mediated transient (from +62±5 to +25±3 BPM). Activation of 5-HT1A receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked anti-tachycardic effect of systemically administered drug, but did not affect basal heart rate. We conclude that tachycardia induced by the restraint stress occurs due to sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT1A receptors attenuates this tachycardia, by suppressing both autonomic effects. At least some relevant receptors are located in the medullary raphe/parapyramidal area.
