Altered in vivo catecholamine release in the hypothalamic paraventricular nucleus of the aged rat

Abstract

The effect of age on basal and stimulated noradrenaline release in the hypothalamic paraventricular nucleus (PVN) of the rat was examined by in vivo microdialysis. Microdialysis probes were inserted into the PVN of 3 and 18 month old anaesthetised Sprague Dawley rats and perfused with a modified Ringer solution. Following four basal 30-min collections, transmitter release was stimulated by perfusion with 100 mM potassium for one collection. After re-equilibration, blood pressure was raised 60 mmHg for 30 min by phenylephrine infusion (1-1.3 mg/kg) then a 2-h recovery period followed. Dialysate collections were injected directly onto a reverse phase HPLC-ECD (HPLC with electrochemical detection). Basal extracellular noradrenaline concentrations were found to be similar in adult and old animals. Basal dihydroxyphenylacetic acid (DOPAC) concentrations were significantly greater in old compared to adult rats (P < 0.05). Potassium depolarisation induced a significant increase in noradrenaline concentrations in both age groups (P < 0.001), however the noradrenaline response to potassium stimulation was significantly reduced in the aged rats (P < 0.05). Potassium-induced decreases in DOPAC and homovanillic acid (HVA) concentrations were seen in both age groups. Following phenylephrine infusion, a modest delayed reduction in noradrenaline levels, which failed to reach statistical significance, was seen. Phenylephrine-induced hypertension was associated with decreased DOPAC and HVA concentrations in adult (P < 0.05) and old (P < 0.05) rats, respectively. These results indicate that ageing is associated with changes in dopaminergic and noradrenergic activity in the PVN of the rat. A reduction in noradrenaline response to maximal stimulation induced by potassium depolarisation was observed with ageing. The alteration in the activity of the catecholaminergic pathways to the PVN induced by phenylephrine infusion appears to be age dependent.

Combined effect of obesity and aging on feeding-induced monoamine release in the rostromedial hypothalamus of the Zucker rat

“…49 Few studies were performed in our region of interest, the PVN, where a decrease in NA release in response to K was observed. 50 These data show a general tendency to a decreased monoamine release with aging, except for DA, and thus are in agreement with the present study with regard to 5-HT, but differ with regard to DA. The reason for this controversy is that some agents such as K , release DA from newly synthesized pools, while others such as tyramine and amphetamine, release DA from vesicular stores by a carrier mediated mechanism.…”

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

“…The degree of stimulation of transmitter release by K + observed in the present study is similar to that seen with in vivo microdialysis procedures for noradrenaline (Badoer et al 1989;Morris et al 1994;Hastings et al 1996) and push-pull superfusion for NPY overflow (Stricker- Krongrad et al 1993;Morris et al 1997b). The technique described in the present study provides the real advantage of enabling release of monoamine and peptide co-transmitters such as NPY to be studied concomitantly.…”

“…We have observed changes in noradrenaline release in aged rats in vivo (Hastings et al 1996), thus comparisons between techniques is difficult and we cannot rule out the possibility that changes in noradrenaline release may result from selective alterations in various noradrenergic projections during ageing which were not reflected in this study using the entire hypothalamus.…”