Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction

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Abstract

The neurochemical changes underlying human emotions and social behavior are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 (Hcrt-1) and melanin concentrating hormone (MCH), measured in the human amygdala. We show that Hcrt-1 levels are maximal during positive emotion, social interaction, and anger, behaviors that induce cataplexy in human narcoleptics. In contrast, MCH levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. MCH levels increase at sleep onset, consistent with a role in sleep induction, whereas Hcrt-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.

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Most cited references 68

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Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

Takeshi Sakurai, Akira Amemiya, Makoto Ishii … (1998)

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Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

T Sakurai, A Amemiya, M Ishii … (1998)

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.

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The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

L de Lecea, T S Kilduff, C Peyron … (1998)

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.