Neuropeptide Y and [Leu,Pro]neuropeptide Y potentiate potassium-induced noradrenaline release in the paraventricular nucleus of the aged rat

This microdialysis study investigated the effects of NPY and the Y₁ selective agonist [Leu³¹,Pro³⁴]NPY on basal and potassium-stimulated noradrenaline release in the PVN of 18-month-old anaesthetised male Sprague–Dawley rats. Microdialysate noradrenaline, DOPAC and HVA concentrations were measured by HPLC after i.c.v. administration of 2 nmol NPY, [Leu³¹,Pro³⁴]NPY or vehicle. [Leu³¹,Pro³⁴]NPY produced a significant 40% reduction in basal noradrenaline concentration (P<0.05). Aged rats had blunted noradrenaline responses to potassium stimulation, however stimulated noradrenaline release was similar in 18-month-old NPY-treated animals and 3-month-old saline treated age controls (2.8 and 3.2 times resting, respectively). [Leu³¹,Pro³⁴]NPY induced a significantly greater release of noradrenaline in response to KCl (5.0 times resting, P<0.05). Thus, in 18-month-old animals with reduced endogenous hypothalamic NPY content, administration of NPY or [Leu³¹,Pro³⁴]NPY increased potassium-induced noradrenaline release to levels seen in 3-month-old rats. This effect may be mediated by an NPY Y₁ receptor.