Hypocretin: the 6 functions of this neurotransmitter

When we think of neurotransmitters, names like serotonin, dopamine, norepinephrine, 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 are of great importance in our functioning as humans. Among them we can find a type of neuropeptide that was only identified in 1998: hypocretins or orexins. In this article, we will briefly introduce what they are and some of the multiple functions in which they are involved.

    What is a hypocretin?

    Hypocretins or orexins are peptides, small molecules composed of chains of amino acids found in large quantities in most animals. These substances were discovered relatively recently (particularly in 1998) and have been shown to have a great influence on a wide variety of functions. The fact that it can be named in two ways is due to the fact that this neurotransmission system was discovered almost simultaneously by two different research teams, with the correspondence between the two observed later.

    In the hypocretines there are mainly two neuropeptides, hypocretins 1 and 2 (Or orexins A and B), which have their corresponding receptors on the membranes of certain cells of the nervous system.

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

    Although the localization of neurons in this system only occurs in the posterior hypothalamus, the hypocretinergic system has a wide effect throughout the brain since the neurons that depart from it have a large number of connections with various areas of this set of organs. These include those who have the limbic system, hypocretin being closely related to emotional processes. It is also related 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 most well-known functions of hypocretines is related to emotion and mood. And they’ve been proven to exist dense connections of hypocretinergic neurons between the hypothalamus and the limbic system. Although it does not generate emotions per se, this neurotransmitter works by maximizing the emotional experience.

    In this sense, the presence of hypocretin appears to be related to experiencing emotions that involve a surge of energyEither be positive like joy or more negative like anger. Likewise, in depressed or stressed patients, a decrease in the level of these neurotransmitters has been observed.

      2. Regulation of sleep / wake cycles

      Awakening and sleep are also largely mediated by hypocretins or orexins, in particular affecting the activation of the vigilance system and the maintenance of the state of vigilance. This in turn is involved in attention span and the use of physical and mental energy and resources.

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

      3. Forgetting and memory: hypocretine in memory

      Another of the many tasks associated with hypocretines is in memory. More precisely, 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. In other words, hypocretines help us to consolidate and hold in memory unpleasant memories (an aspect which can still seem experimentally aversive, is functionally useful in allowing us to move away from the source of this stimulation).

        4. Learning

        Directly derived from the point above, we can consider that the hypocretins possess a role of great relevance in the implementation of learning and conditioning, Especially when it comes to learning about fear.

        5. Ingestion

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

        6. Gratification and pleasure

        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 many existing addictions, both in terms of drugs and in terms of sex or food.

        Disorders to which they are linked

        As we have said, hypocretines have multiple functions of great importance to humans. For this reason, the dysfunction of the hypocretinergic system can have important consequences on our conduct, there is a link between the action of this neurotransmitter and certain disorders. Some of them are as follows.

        1. Narcolepsy

        One of the main research related to hypocretins concerns its effect on circadian rhythms and wakefulness. Insufficient reduction or the presence of hypocretins makes it difficult to stay awake, a deficiency of these substances has been linked to the origin of narcolepsy (Although much more research is needed in this regard).

        2. Outbuildings

        Another major research that has been conducted shows that hypocretins are linked to addiction and relapses. hypocretines they are linked to anxiety and motivation to reach the elements that make us feel pleasure and well-being, being a biological substrate that has a certain influence by facilitating the possibility of relapses in addictions.

        3. Depression

        Different research seems to indicate that the presence of a high level of hypocretins corresponds to energetic moods, which it could be used in the future to make drugs for passivity and lack of energy clean of depression.

        4. Anxiety and stress-related disorders

        It has also been observed that hypocretins are related to coding and maintaining aversive memories and regulating fear. High levels make it difficult for fear to be extinguished, for example, in a phobia or post-traumatic stress disorder.

        Bibliographical references:

        • Baumann, CR and Bassetti, CL (2005). Hypocretins (Orexins): Clinical impact of the discovery of a neurotransmitter. Sleep Medicine Opinion 9 (4): 253-268.
        • Flores, A .; Valls-Comamala, V .; Costa, G .; Saravia, R .; Maldonado, T .; Berrendero, F. (2014). The hypocretin / orexin system is involved in the extinction of fear memories. Neuropsychopharmacology. 39: 2732-2741.
        • Plaça-Zabala, A .; Martín-García, E .; by Lecea, L .; Maldonado, R .; Berrendero, F. (2010). The hypocretins regulate the anxiogenic effects of nicotine and induce the reestablishment of nicotine seeking behavior. Journal of Neuroscience, 30: 2300-2310.
        • Siegel JM (1999). Narcolepsy: a key role for hypocretins (orexins). Cell, 98: 409-412.
        • Siegel, JM; Moore, MD; Thannickal, T. and Nienhuis, RS (2001) A brief history of hypocretin / orexin and narcolepsy. Neuropsychopharmacology, 25: 514-520.
        • Schwartz JR, Roth T. (2008). Neurophysiology of sleep and wakefulness: basic sciences and clinical implications. Curr Neuropharmacol. 6: 367-78.

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