NK 3 receptor
The selective NK 3 receptor agonist Senktide excites 24 of 31 dopaminergic neurons in the substantia nigra pars compacta in a concentration-dependent manner. The effective concentration range is between 3 to 3000 nm. The mean EC 50 for Senktide is 41.2±9 nm (n=5).
I.c.v. injection of Senktide causes a dose-dependent increase in total distance traveled (F 6,72 =6.344, P<0.001). This increase reaches statistical significance compare to the vehicle-treated group at 0.06 nmol and higher. The Senktide-induced increase in locomotor activity brought about by 0.1 nmol of Senktide is significantly and dose-dependently decreased by the tachykinin NK 3 receptor antagonists talnetant at 30 mg/kg and SB222200 at 30 mg/kg, but not by osanetant, when tested in parallel in a single experiment (F 7,78 =10.32, P<0.001), although a non-significant reduction is observed. However, when tested using another vehicle (Vitamin E and glycofurol), osanetant does decrease activity significantly compare to Senktide-treated gerbils (F 2,30 =10.10, P<0.001).