Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism

Neuropeptide Y (NPY) has been reported to profoundly influence and regulate brain circuits involved in a number of behaviours, like anxiety, alcohol intake, pain and energy homeostasis. Here we show that NPY increases sedation induced by different types of anaesthetics through interactions with the Y-1 receptor. Consistently, in Y-1(-/-) (homozygote knockout) mice NPY does not potentiate the pentobarbital-induced sedation. Similar results were obtained for avertin but not for ketalar- (NMDA antagonist) induced sedation. Local microinjection of NPY exhibited the strongest potentiating effect on pentobarbital-induced sedation in the posterior hypothalamic area and Y-1 expression was found in the dorsal-premammillary and medial part of medial mammillary nuclei. These results show that Y-1 is essential for NPY-Induced enhancement of sedation and place this activity of NPY in the posterior hypothalamic area, a region of the brain previously implicated in the regulation of the wake-sleep cycle.