Hypocretin: the 6 functions of this neurotransmitter

This type of neurotransmitter is involved in our motivation and emotion regulation.

When we think of neurotransmitters, names such as serotonin, dopamine, noradrenaline, glutamate, GABA or acetylcholine usually come to mind. Histamine and melatonin are also widely known.

However, there are many other substances that act as neurotransmitters and 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: the hypocretins or orexins. In this article we will briefly introduce what they are and some of the multiple functions in which they participate.

What is a hypocretin?

The hypocretins or orexins are peptides, small molecules composed of amino acid chains that are found in large quantities in most animals. These substances were discovered relatively recently (in 1998) and have been shown to have a great influence on a wide variety of functions. The fact that they can be referred to in two ways is due to the fact that this neurotransmitter system was discovered practically simultaneously by two different research teams, and the correspondence between the two was subsequently observed.

Within the hypocretins we can find mainly two neuropeptides, hypocretins 1 and 2 (or orexins A and B). (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 form a system called the hypocretinergic system..

Although the localization of the neurons of this system is only in the posterior hypothalamus, the hypocretinergic system has a broad effect on the whole brain, the hypocretinergic system has a broad effect on the whole brain, since the neurons since the neurons that originate from it have a large number of connections with various areas of this group of organs. Among them the existing ones with the limbic system stand out, being the hypocretin very related to the 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 little known by most of the population, hypocretins play a very important role in a large number of functions and processes relevant to our behavior. Let us see what they are.

1. Emotion and mood regulation

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

In this sense, the presence of hypocretin seems to be linked to the experience of emotions. linked to the experience of emotions that entail a surge of energy, either positiveeither positive, such as joy, or more negative, such as anger. Similarly, in depressed or stressed patients, a decrease in the level of these neurotransmitters has been observed.

Regulation of sleep/wake cycles 2.

Wakefulness and sleep are also mediated to a large extent by hypocretins or orexins, namely. affecting the activation of the waking system and the maintenance of wakefulness.. This in turn is involved in the capacity of attention and the use of energy and physical and mental resources.

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

3. Forgetfulness and memory: hypocretin in memory

Another of the multiple tasks associated with hypocretins is found in memory. Specifically, experiments on rodents have shown that blocking the receptors of this type of peptides generate the disappearance of aversive memories.. In other words, hypocretins help us to consolidate and maintain unpleasant memories in our memory (an aspect that, although experientially it may seem aversive, is functionally useful by allowing us to move away from the source of such stimulation).

4. Learning

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

5. Ingestion

Another of the basic functions in which hypocretins participate is in the intake. It has been observed that these molecules play a relevant role in explaining why we seek food and why we have to eat. why we search for food and why we crave it.. The synthesis of hypocretins is activated by the action of ghrelin and inhibited by leptin, which are known to act to generate hunger or satiety respectively. It is also suspected that it is their action that generates the link between food and sleep.

6. Gratification and pleasure

Orexin or hypocretin is strongly linked to emotions and the sensation of pleasure, as well as the desire to obtain it. This is what happens with the numerous existing addictions, at the level of drugs as well as at the level of sex or food..

Disorders to which they are linked

As we have said, the hypocretins have multiple functions of great relevance for the human being. Therefore, the dysfunction of the hypocretinergic system can have relevant consequences on 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 research related to hypocretins has to do with their effect on circadian rhythms and wakefulness. The reduction or insufficient presence of hypocretins makes it difficult to stay awake, a deficit of these substances has been linked to the origin of narcolepsy (although much more research is needed). (although much more research is needed).

2. Addictions

Another major research that has been carried out shows that hypocretins are related to addiction and relapse. Hypocretins are linked to cravings and motivation to get the things that make us feel to obtain the elements that make us feel pleasure and well-being, being a biological substrate that has certain influence when it comes to facilitating the possibility of relapse in addictions.

3. Depression

Different investigations seem to show 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. This could be used in the future to develop drugs against the passivity and lack of energy of depression. and lack of energy characteristic of depression.

4. Anxiety and stress-related disorders

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

Bibliographical 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.; de Lecea, L.; Maldonado, R.; Berrendero, F. (2010). Hypocretins Regulate the Anxiogenic-Like Effects of Nicotine and induce 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.