Abstract
Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR). High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v.) injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir) neurons that also bear NPSR. NPS (0.1–1 nmol) i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val5]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON), piriform cortex (Pir), ventral tenia tecta (VTT), the anterior cortical amygdaloid nucleus (ACo) and lateral entorhinal cortex (LEnt). The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice.
Highlights
Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem
The present study firstly demonstrated that i.c.v. administration of NPS in mice facilitated the olfactory abilities by reducing the latency to find the buried food and increasing olfactory differentiation of different odors (Fig. 2–3)
0.5 nmol of NPS would probably already activate maximally its brain targets, because in this dose, NPS reduced the latency most to find the buried food, and significantly promoted the dishabituation and habituation to all test odors. These results indicate that NPS could enhance the ability to smell volatile odors and to detect and differentiate the different odors
Summary
Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem. NPS precursor mRNA in the rat is expressed in a group of neurons located between the locus ceruleus (LC) and Barrington’s nucleus, the principle sensory trigeminal nucleus, and the lateral parabrachial nucleus [1]. NPSR mRNA is found widely distributed in the rat and mouse brain, mainly in the olfactory cortex, cerebral cortex, thalamus, hypothalamus, amygdala, and subculum [1,2,3,4]. This profile of NPSR mRNA expression suggests involvement of NPS-NPSR system in the regulation of multiple central functions. NPS is involved in antinociception [8,9], fear expression and extinction [10] and memory processes in mice [11,12], and facilitates relapse to cocaine seeking in rats [13]
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