Activation of 5-HT(1A) receptors attenuates tachycardia induced by restraint stress in rats.
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.
Ngampramuan
Sukonthar
S
Neuro-Behavioural Biology Centre, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Nakron Pathom, Thailand.
Baumert
Mathias
M
Beig
Mirza Irfan
MI
Kotchabhakdi
Naiphinich
N
Nalivaiko
Eugene
E
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
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