Selective blockade of neurokinin (NK)(1) receptors facilitates the activity of adrenergic pathways projecting to frontal cortex and dorsal hippocampus in rats

The selective NK1 receptor antagonist, GR205,171 (2.5-40.0 mg/kg, i.p.), do se-dependently elevated dialysate levels of noradrenaline (NA), but not ser otonin (5-HT), in the frontal cortex of freely moving rats. This action was exerted stereospecifically inasmuch as its less active isomer, GR226,206, was ineffective. In the dorsal hippocampus, GR205,171 (but not GR226,206) a lso significantly increased dialysate levels of NA, whereas levels of 5-HT were unaffected. Further, in anaesthetized rats, GR205,171 dose-dependently (1.0-4.0 mg/kg, i.v.) increased the firing rate of adrenergic perikarya in the locus coeruleus. In contrast, their activity was not modified by GR226 ,206. These findings indicate that selective blockade of NK1 receptors enha nces the activity of ascending adrenergic pathways in rats. Adrenergic mech anisms may, thus, be involved in the potential antidepressant and other fun ctional properties of NK1 receptor antagonists.