Release of 3H-noradrenaline by excitatory amino acids from rat mediobasal hypothalamus and the influence of aging

Abstract

The present study was designed to analyze the effects of glutamate (GLU) and its agonists on the release of noradrenaline (NA) from the mediobasal region of rat hypothalamus (MBH). Slices from hypothalamus were loaded in vitro with 3H-NA and thereafter exposed to GLU and the glutamate agonists N- methyl- d-aspartic acid (NMDA) and kainate (KA), in superfusion chambers. GLU evoked a significant 3H-NA release in a concentration-dependent manner. The EC 50 was 35 mM. 6-Cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a non-NMDA selective antagonist, and amino-7-phosphonoheptanoic acid (AP 7), a NMDA selective antagonist, both decreased the GLU-evoked response to about 50% of its value. NMDA, superfused in Mg 2+-free Krebs-Ringer, exhibited a greater potency than GLU with an EC 50 = 124 μM. KA was also able to evoke 3H-NA release, although overall responses to KA were lower than those of NMDA. The maximal response to KA was a 36% increase of release at a concentration of 200 μM. The effect of KA was blunted by CNQX. NMDA-induced 3H-NA release was progressively altered with age. In old rats (16–18 months) and middle-aged rats (10 months), responses to 200 μM NMDA were decreased respect to young (4 months) male rats. These results show that NMDA and KA receptors mediate the excitatory effects of GLU on NA release from nerve terminals in the MBH and suggest that GLU, in association with NA, participates in the complex mechanisms that regulate neuroendocrine functions. In addition, the age-related changes in NA responsiveness point to a GLU contribution on the maintenance of the reproductive status.