RELEASE OF H-3 NORADRENALINE BY EXCITATORY AMINO-ACIDS FROM RAT MEDIOBASAL HYPOTHALAMUS AND THE INFLUENCE OF AGING

The present study was designed to analyze the effects of glutamate (GL U) and its agonists on the release of noradrenaline (NA) from the medi obasal region of rat hypothalamus (MBH). Slices from hypothalamus were loaded in vitro with H-3-NA and thereafter exposed to GLU and the glu tamate agonists N-methyl-D-aspartic acid (NMDA) and kainate (KA), in s uperfusion chambers. GLU evoked a significant H-3-NA release in a conc entration-dependent manner. The EC(50) was 35 mM. 6-Cyano-7-nitro-quin oxaline-2,3-dione (CNQX), a non-NMDA selective antagonist, and amino-7 -phosphonoheptanoic acid (AP 7), a NMDA selective antagonist, both dec reased the GLU-evoked response to about 50% of its value. NMDA, superf used in Mg2+-free Krebs-Ringer, exhibited a greater potency than GLU w ith an EC(50) = 124 mu M. KA was also able to evoke H-3-NA release, al though overall responses to KA were lower than those of NMDA. The maxi mal response to KA was a 36% increase of release at a concentration of 200 mu M. The effect of KA was blunted by CNQX. NMDA-induced H-3-NA r elease was progressively altered with age. In old rats (16-18 months) and middle-aged rats (10 months), responses to 200 mu M NMDA were decr eased respect to young (4 months) male rats. These results show that N MDA and KA receptors mediate the excitatory effects of GLU on NA relea se from nerve terminals in the MBH and suggest that GLU, in associatio n with NA, participates in the complex mechanisms that regulate neuroe ndocrine functions. In addition, the age-related changes in NA respons iveness point to a GLU contribution on the maintenance of the reproduc tive status.