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

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.