In vitro studies of endogenous noradrenaline and NPY overflow from the rat hypothalamus during maturation and ageing

Abstract

Marked changes in brain monoamine content and NPY content occur during maturation and ageing. Earlier in vivo studies in our laboratory have reported blunted K⁺ stimulated noradrenaline release and reduced NPY overflow in aged animals using microdialysis and push pull techniques. In this study, in vitro superfusion techniques were established to measure endogenous noradrenaline, NPY, DOPAC and 5-HIAA overflow from the hypothalamus of 1, 5 and 16 month old Sprague-Dawley rats. A period of high K⁺ (56 mM) stimulation was carried out to elicit maximal release. Basal noradrenaline overflow was similar in all age groups of rats and during K⁺-induced depolarisation similar 3–4 fold increases were observed. On the other hand, basal and K⁺ stimulated NPY overflow were significantly greater in the adult rats compared to 1 month and 16 month old rats. Despite differences in absolute NPY overflow, the relative increase over resting was not significantly different across age groups. The molar quantities of hypothalamic NPY overflow at rest and under K⁺ stimulated conditions were three orders of magnitude lower than noradrenaline. Results of these studies suggest that both NPY and noradrenaline can be released from a similar hypothalamic pool. Basal and K⁺-evoked DOPAC and 5-HIAA overflow were similar between the 3 age groups. Thus the overflow of hypothalamic noradrenaline, DOPAC and 5-HIAA under in vitro conditions was not altered from 1 to 16 months. In contrast, 5 month old rats had significantly higher NPY overflow than the other age groups (P < 0.05), consistent with a reported decline in NPY content with advanced age. Hypothalamic noradrenaline overflow was not affected by ageing, suggesting that a selective loss of NPY in the arcuo-PVN projection, or other projections to the hypothalamus with ageing may contribute to the reduction in NPY overflow in aged rats.