STIMULATION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE DORSOMEDIAL HYPOTHALAMUS ELEVATES HEART-RATE IN RATS

This study examined the potential role of metabotropic glutamate recep tors (mGluRs) in the dorsomedial hypothalamus (DMH) by assessing the c ardiovascular effects of microinjecting the agonist trans-1-aminocyclo pentane-1,3-dicarboxylate (tACPD) into this region in urethan-anesthet ized rats. Dose-related tachycardia was observed after unilateral micr oinjection 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 mGl uRs linked to phosphoinositide hydrolysis, resulted in increases in he art rate that correlated closely in magnitude to those seen after inje ction of the same dose of 1S,3R-tACPD. Coinjection of the N-methyl-D-a spartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic ac id, given at dos es shown to elicit selective blockade of NMDA ionotro pic glutamate receptors, reduced the increase in heart rate evoked by 100 pmol 1S,3R-tACPD alone. Thus the DMH contains functional mGluRs, a nd stimulation of these receptors activates the same sympathoexcitator y mechanism characterized previously to provoke dose-related tachycard ia.