Abstract

Both orexin and neurotensin are expressed in the lateral hypothalamic area (LHA) and have been implicated in the regulation of feeding, motor activity and the reward system. A double label immunofluorescence and in situ hybridization studies showed that neurotensin colocalizes with orexin in neurons of the LHA. Pharmacological studies suggested that neurotensin excites orexin-producing neurons (orexin neurons) through activation of neurotensin receptor-2 (NTSR-2) and non-selective cation channels. In situ hybridization study showed that most orexin neurons express neurotensin receptor-2 mRNA but not neurotensin receptor-1 (Ntsr-1) mRNA. Immunohistochemical studies showed that neurotensin-immunoreactive fibers make appositions to orexin neurons. A neurotensin receptor antagonist decreased Fos expression in orexin neurons and wakefulness time in wild type mice when administered intraperitoneally. However, the antagonist did not evoke any effect on these parameters in orexin neuron-ablated mice. These observations suggest the importance of neurotensin in maintaining activity of orexin neurons. The evidence presented here expands our understanding of the regulatory mechanism of orexin neurons.

Highlights

  • Neurotensin is a 13 amino-acid residue neuropeptide implicated in neuroendocrine function, feeding behavior and the reward system

  • Immunostaining showed that many neurotensin-containing cells were observed in the lateral hypothalamic area (LHA), zona incerta (ZI) and central nucleus of the amygdala (CeA) (Figure 1A)

  • This study revealed that 82% of orexin neurons in the LHA expressed neurotensin

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Summary

Introduction

Neurotensin is a 13 amino-acid residue neuropeptide implicated in neuroendocrine function, feeding behavior and the reward system. Orexin A and orexin B ( known as hypocretin 1 and hypocretin 2) are neuropeptides that are expressed in a population of neurons in the lateral hypothalamic area (LHA) [6,7]. Disruption of this neuropeptide system causes narcolepsy in human and animals, suggesting that orexins are crucial regulators of sleep and wakefulness [8]. Orexin neurons contain other peptides including dynorphin, and neuronal activity-regulated pentraxin (Narp) [23,24,25] These factors may play cooperative roles with orexin, orexin is likely to play a central role in the function of these neurons, because orexin2/2 mice and orexin neuron-ablated mice show almost the same phenotype [26]. We show that neurontensin plays an important role in maintenance of activity of orexin neurons and physiological regulation of sleep/wakefulness states

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