Stimulation of metabotropic glutamate receptors in the dorsomedial
hypothalamus elevates heart rate in rats.
Dimicco, Joseph A., and Amy J. Monroe.
Department of Pharmacology and Toxicology, Indiana University
School of Medicine, Indianapolis, Indiana 46202-5120
APStracts 2:0348R, 1995.
This study examined the potential role of metabotropic glutamate
receptors (mGluRs) in the dorsomedial hypothalamus (DMH) by assessing
the cardiovascular effects of microinjecting the agonist trans-1
-aminocyclopentane-1,3-dicarboxylate (tACPD) into this region in
urethane-anesthetized rats. Dose-related tachycardia was observed
after unilateral microinjection of 1S,3R-tACPD 10-200 pmol/50 nL, but
not after injection of 1R,3S-tACPD, which has been reported to have
little or no activity at mGluRs. Microinjection of
dihydroxyphenylglycine, an agonist at mGluRs linked to
phosphoinositide hydrolysis, resulted in increases in heart rate that
correlated closely in magnitude to those seen after injection of the
same dose of 1S,3R-tACPD. Coinjection of the NMDA receptor antagonist
AP5, given at doses shown to elicit selective blockade of NMDA
ionotropic glutamate receptors, reduced the increase in heart rate
evoked by 100 pmol 1S,3R-tACPD alone. Thus, the DMH contains
functional mGluRs, and stimulation of these receptors activates the
same sympathoexcitatory mechanism characterized previously to provoke
dose-related tachycardia.
Received 26 July 1995; accepted in final form 11 December 1995.
APS Manuscript Number R462-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95