Neuropeptide Y alters sedation through a hypothalamic Y₁‐mediated mechanism

Abstract

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 Y1 receptor. Consistently, in Y1-/- (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 Y1 expression was found in the dorsal-premammillary and medial part of medial mammillary nuclei. These results show that Y1 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.

Neuropeptide Y Inhibits Hypocretin/Orexin Neurons by Multiple Presynaptic and Postsynaptic Mechanisms: Tonic Depression of the Hypothalamic Arousal System

“…Consistent with this, NPY has been postulated to enhance sedation after application to the LH, the region where hypocretin neurons are found. This action involved a decrease of wakefulness in pentobarbital-or avertin-induced sedation (Naveilhan et al, 2001), suggesting that this effect may be explained in part by NPY inhibition of the arousal-enhancing hypocretin cells. Similarly, intracranial application of NPY may reduce anxiety (Ehlers et al, 1997).…”

“…NPY could play additional roles in modulating hypocretin cells. NPY application into the region of the hypothalamus where hypocretin cells are located enhances the soporific effect of anesthetics (Naveilhan et al, 2001); NPY also has anxiolytic properties when injected intracranially (Ehlers et al, 1997), raising the question whether hypocretin cells may be involved in these effects. Medullary neurons send NPY projections to the hypothalamus potentially conveying sensory and baroreceptive information from the gut and heart Verberne et al, 1999).…”

Addiction and arousal: The hypocretin connection

“…[35]. Interestingly, icv administration of NPY increases sedation [36] and has anxiolytic activity in response to some stimuli [37][38][39]. NPY potently hyperpolarizes hypocretin neurons in vitro [40].…”

Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

“…In spite of the mutual exclusivity of these pathways and the behaviors they mediate, it is intriguing that the sensitized effects of NPY during ethanol abstinence extend to multiple behaviors. More specifically, the orexigenic effects of NPY are mediated by the PVN (Stanley et al, 1985), the sedative effects by the posterior hypothalamic nucleus (Naveilhan et al, 2001), and the CeA mediates the suppressive effects of NPY on anxiety-like behavior (Heilig et al, 1993) and possibly ethanol drinking (Pandey et al, 2005); the effects of NPY on most, if not all, of these behaviors is augmented following periods of ethanol abstinence (Gilpin et al, 2005;Rimondini et al, 2005). Therefore, Voluntary consumption by P rats of amounts of ethanol similar to those in the present study produce pharmacologically significant blood ethanol levels, ranging from 50 to 200 mg% (Li et al, 1979;Murphy et al, 1986), and these levels of consumption by P rats produce tolerance to the effects of ethanol (Gatto et al, 1987; and perhaps even dependence (Kampov-Polevoy et al, 2000;Waller et al, 1982).…”