The selective neurokinin (NK)(1) antagonist, GR205,171, stereospecifically enhances mesocortical dopaminergic transmission in the rat: a combined dialysis and electrophysiological study.

Upon acute, systemic administration, the selective, non-peptidergic NK(1) receptor antagonist, GR205,171, dose-dependently enhanced the firing rate of ventrotegmental dopaminergic neurones. Dialysate levels of dopamine were increased in the frontal cortex, but not in the striatum and nucleus accumbens, of conscious rats. These actions were stereospecific in that its less-active isomer, GR226,206, was ineffective. Further, they were selective for dopaminergic pathways inasmuch as the firing rate of dorsal raphe serotonergic neurones and dialysate levels of serotonin were unaffected by GR205,171. Activation of mesocortical dopaminergic pathways may be involved in the influence of NK(1) antagonists upon mood.