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Hypocretin: the 6 functions of this neurotransmitter

Hypocretin: the 6 functions of this neurotransmitter

July 27, 2022

When we think of neurotransmitters, we usually come up with names like serotonin, dopamine, noradrenaline, glutamate, GABA or acetylcholine. Histamine and melatonin are also widely known.

However, there are many other substances that act as neurotransmitters and that have great relevance in our functioning as human beings. Among them we can find a type of neuropeptide that has not been identified until 1998: hypocretins or orexins . In this article, we will briefly introduce what they are and some of the multiple functions in which they participate.

  • Related article: "Types of neurotransmitters: functions and classification"

What is a hypocretin?

The hypocretins or orexins are peptides, small molecules composed of chains of amino acids that are found in a large amount in most animals. These are substances discovered relatively recently (specifically in 1998) and which have been shown to have a great influence on a wide variety of functions. The fact of being able to be named in two ways is due to the fact that this neurotransmission system was discovered practically simultaneously by two different research teams, observing the correspondence between both later.


Within the hypocretins We can mainly find two neuropeptides, hypocretins 1 and 2 (or orexins A and B), which have their corresponding receptors in the membranes of some of the cells of the nervous system.

As with other hormones such as dopamine, the neurons that synthesize and use this type of neurotransmitter They make up a system, called the hypocretinergic system .

Although the location of the neurons of this system occurs only in the posterior hypothalamus, the hypocretinergic system has a wide effect on the whole brain since the neurons that depart from it have a large number of connections with different areas of this set of organs. Among them, those existing with the limbic system stand out, with hypocretin being closely related to emotional processes. It is also linked to the ascending reticular system, being very relevant in processes such as sleep and wakefulness.


Functions of these peptides

Although relatively unknown to most of the population, hypocretins play a very important role in a large number of functions and processes relevant to our behavior. Let's see what they are.

1. Regulation of emotions and mood

One of the best known functions of hypocretins has to do with emotion and mood. And it is proven that there are dense connections of hypocretinergic neurons between the hypothalamus and the limbic system . Although it does not generate the emotions themselves, this neurotransmitter works by maximizing the emotional experience.

In this sense the presence of hypocretin seems to be linked to the experience of emotions that suppose a rebound of energy , either positive as joy or other more negative as anger. In the same way, in depressed or stressed patients a decrease in the level of said neurotransmitters has been observed.


  • You may be interested: "Are there several types of depression?"

2. Regulation of sleep / wake cycles

Waking and sleep are also largely mediated by hypocretins or orexins, specifically affecting the activation of the vigil system and the maintenance of the vigil state . This is in turn involved in the attention capacity and the use of energy and physical and mental resources.

A lower concentration than necessary will generate alterations in this maintenance, finding this factor linked to the disorder known as narcolepsy (in fact it is one of the possible biological explanations of the disorder).

3. Forgetting and remembering: hypocretin in memory

Another of the multiple tasks associated with hypocretins is found in memory. Specifically, in experiments carried out with rodents it is observed that the blockade of the receptors of this type of peptides they generate the disappearance of aversive memories . That is, hypocretins help us to consolidate and maintain unpleasant memories (an aspect that although experientially may seem aversive, is functionally useful in allowing us to get away from the source of such stimulation).

  • Related article: "Types of memory: how does memory store the human brain?

4. Learning

Directly derived from the previous point we can consider that hypocretins have a role of great relevance in the establishment of learning and conditioning , especially with regard to learning based on fear.

5. Ingestion

Another of the basic functions in which hypocretins participate is in the intake.It has been observed that these molecules have a relevant role when it comes to explaining why do we look for food and have the urge to eat . The synthesis of hypocretins is activated by the action of ghrelin and inhibited by leptin, which are known for their action when generating respectively hunger or satiety. It is also suspected that it is their actions that generate a connection between food and sleep.

6. Gratification and pleasure

The orexin or hypocretin is strongly linked to emotions and the feeling of pleasure, as well as the desire to achieve it. This is what happens with the numerous existing addictions, both at the level of drugs and at the level of sex or food .

Disorders to which they are linked

As we have said, hypocretins have multiple functions of great relevance for humans. Therefore, dysfunction of the hypocretinergic system can have relevant consequences to our behavior, There is a certain link between the action of this neurotransmitter and some disorders . Some of them are the following.

1. Narcolepsy

One of the main investigations related to hypocretins has to do with its effect on circadian rhythms and wakefulness. The reduction or insufficient presence of hypocretins makes it difficult to stay awake, a deficit of these substances having been linked to the origin of narcolepsy (although much more research is required).

2. Addictions

Another major research that has been carried out reflects that hypocretins are related to addiction and relapse. The hypocretins they are linked to craving and motivation to obtain the elements that make us feel pleasure and wellbeing, being a biological substrate that has some influence at the time of facilitating the possibility of relapses in addictions.

3. Depression

Different investigations seem to reflect that the presence of a high level of hypocretins corresponds to energetic moods, which could be used in the future to develop drugs against passivity and lack of energy proper to depression.

4. Anxiety and stress-related disorders

Likewise, it has been observed that hypocretins are related to coding and maintenance of aversive memories and the regulation of fear . High levels make it difficult to extinguish fear, for example, in a phobia or post-traumatic stress disorder.

Bibliographic references:

  • Baumann, C.R. & Bassetti, C.L. (2005). Hypocretins (Orexins): Clinical Impact of the Discovery of a Neurotransmitter. Sleep Medicine Reviews 9 (4): 253-268.
  • Flores, A .; Valls-Comamala, V .; Costa, G .; Saravia, R .; Maldonado, T .; Berrendero, F. (2014). The hypocretin / orexin system mediates the extinction of fear memories. Neuropsychopharmacology. 39: 2732-2741.
  • Plaza-Zabala, A .; Martín-García, E .; from Lecea, L .; Maldonado, R .; Berrendero, F. (2010). Hypocretins Regulate the Anxiogenic-Like Effects of Nicotine and induces Reinstatement of Nicotine-Seeking Behavior. Journal of Neuroscience, 30: 2300-2310.
  • Siegel J.M. (1999). Narcolepsy: A key role for hypocretins (orexins). Cell, 98: 409-412.
  • Siegel, J.M .; Moore, M.D .; Thannickal, T. & Nienhuis, R.S. (2001) A brief history of hypocretin / orexin and narcolepsy. Neuropsychopharmacology, 25: 514-520.
  • Schwartz JR, Roth T. (2008). Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 6: 367-78.

To Sleep, Perchance to Dream - Crash Course Psychology #9 (July 2022).


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