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 that have great relevance to 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 hypocrite?

Hypocretins or orexins are peptides, small molecules composed of chains of amino acids that are found in large numbers in most animals. These substances were discovered relatively recently (in 1998) and have been found to have a strong influence on a wide range of functions. The fact that they can be named in two ways is due to the fact that this neurotransmission system was discovered almost 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), which have their corresponding receptors on 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 hypocretinal system .

Despite the fact that the location of the neurons of this system is only in the posterior hypothalamus, the hypocretinergic system has a broad effect on the whole brain since the neurons that start from it have a large number of connections with various 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 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’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. It has been proven that there are dense connections of hypocretinal 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 that suppose an increase of energy , either positive ones such as joy or more negative ones such as anger. Similarly, in depressed or stressed patients a decrease in the level of these neurotransmitters has been observed.

2. Regulation of sleep/wake cycles

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

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

3. Forgetting and remembering: the hypocretin in memory

Another of the many tasks associated with hypocretins is found in memory. Specifically, in experiments carried out with rodents, it has been observed that the blockage of the receptors of this type of peptides generates the disappearance of aversive memories . In other words, hypocretins help us to consolidate and maintain in our memory unpleasant memories (an aspect that, although it may seem experiential, is functionally useful in allowing us to move away from the source of such stimulation).

4. Learning

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

5. Intake

Another of the basic functions in which hypocretins are involved is intake. It has been observed that these molecules play a relevant role in explaining why we forage for food and have the craving to eat . The synthesis of hypocretins is activated by the action of ghrelin and inhibited by leptin, both of which are known to act on generating 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 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 to human beings. Therefore, the dysfunction of the hypocretinal system may have relevant consequences for our behavior , and 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 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 having been related to the origin of narcolepsy (although much more research is needed in this regard).

2. Addictions

Another major research that has been carried out reflects that hypocretins are related to addiction and relapse. Hypocretins are linked to craving and motivation to achieve 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 relapses into addictions.

3. Depression

Different research seems 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 the passivity and lack of energy characteristic of depression.

4. Anxiety and stress-related disorders

It has also been observed that hypocretins are related to the coding and maintenance of aversive memories and the regulation of fear . High levels make it difficult to extinguish the fear, for example, in a phobia or a 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). El sistema de hipocretina/orexina media la extinción de los recuerdos de miedo. Neuropsicofarmacología. 39: 2732-2741.
  • Plaza-Zabala, A.; Martín-García, E.; de Lecea, L.; Maldonado, R.; Berrendero, F. (2010). Las hipocretinas regulan los efectos ansiógenos de la nicotina e inducen a la reinstauración de la conducta de búsqueda de nicotina. Journal of Neuroscience, 30: 2300-2310.
  • Siegel J.M. (1999). Narcolepsia: Un papel clave para las hipocretinas (orexinas). Célula, 98: 409-412.
  • Siegel, J.M.; Moore, M.D.; Thannickal, T. & Nienhuis, R.S. (2001) Una breve historia de la hipocretina/orexina y la narcolepsia. Neuropsicofarmacología, 25: 514-520.
  • Schwartz JR, Roth T. (2008). Neurofisiología del sueño y la vigilia: ciencia básica e implicaciones clínicas. Curr Neuropharmacol. 6: 367-78.