Effects of ageing on tachykinin function in the basal ganglia

The effects of ageing on tachykinin-induced behaviours and tachykinin receptors were investigated in the rat. Infusion of the NK-3 tachykinin agonist senktide (0.25, 0.5 and 1 nmol) into the substantia nigra induced locomotion in young (4-6 months) animals but this response was attenuated in middle-aged (12 months) and old (27 months) animals. In contrast, senktide-induced wet dog shakes were not significantly affected by age. In the ventral tegmental area, senktide induced locomotion and wet dog shakes with bell-shaped dose-response curves which were unaffected by age. Senktide suppressed grooming but the effect reached significance in the older animals only. Quantitative receptor autoradiography revealed no effect of age on NK-1 tachykinin receptor density in the striatum while NK-3 receptor density declined in the ventrolateral striatum and to a nonsignificant degree in the substantia nigra but not in other striatal subregions or the ventral tegmental area. We conclude that ageing of the nervous system is not associated with widespread changes in tachykinin binding but differences in behavioural response to tachykinin agonists may reflect changes in other transmitter systems which respond to tachykinin input.