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SLEEP: Neurotransmitters


Beneficial sleep occurs when neurotransmitters are optimized in the brain. While there are a number of important players in this symphony we will concentrate on the following in this post: gamma-aminobutyric acid (GABA), glutamate, melatonin, cortisol, adenosine, serotonin, acetylcholine and histamine.


GABA is the primary inhibitory neurotransmitter in the central nervous system. Inhibitory neurotransmitters are important from a sleep perspective since they calm the brain and help to induce a state of reduced electrical activity in the brain. GABA promotes deep, slow wave (delta wave) sleep which occurs during Stage 3 of sleep. GABA is also necessary for non-REM (NREM) sleep and reduces expression of cortisol (see below).


Glutamate is the primary excitatory neurotransmitter in the brain. Since glutamate is excitatory it must be reduced for quality sleep. Coincidentally, GABA is metabolized and produced from glutamate. Thus, when GABA is formed from glutamate, there is a doubly beneficial effect to inducing sleep through reduction of glutamate.


Melatonin is a neurotransmitter, hormone and anti-oxidant that is primarily produced as a metabolite of serotonin, the majority of which is located in the gut. However, it is also produced in the pineal gland and is necessary for deep, quality slow wave sleep. Unfortunately, melatonin production decreases with age.


Cortisol is a corticosteroid hormone that is produced in the adrenal glands. It is normally elevated during the morning and is our “get up and go” hormone. It must be reduced during sleep and its production should be inverse to melatonin. Indeed, elevated cortisol or cortisol spikes during the evening can be the cause of poor or reduced sleep. Baseline cortisol tends to increase with age and even more so in women. As stated above cortisol is reduced by production of GABA. This is accomplished via reduction of corticotropin releasing hormone (CRH) from the hypothalamus thus reducing adrenocorticotropic hormone (ACTH) from the pituitary which in turn reduces production of cortisol in the adrenals.


Adenosine is a neuromodulator that suppresses arousal and promotes sleep. Thus, in general, it has an inhibitory effect on the central nervous system. An elevation in activity of adenosine in the CNS will lead to a relative decrease of glutamate and dopamine. This will result in decreased arousal or wakefulness. Thus, biologically elevated adenosine in the brain induces sleep.


Serotonin is an important neurotransmitter involved in a number of different metabolic processes that influence mood, emotion and behavior. While serotonin influences wakefulness it is also involved in the initiation or triggering of sleep and also induces and promotes deep slow wave sleep or non-REM sleep. Low levels of serotonin can disrupt sleep and induce sleep disorders such as insomnia. Conversely serotonin acts an inhibitor to REM sleep.


Acetylcholine is a neurotransmitter that promotes REM sleep. In fact, as serotonin drops in the brain, acetylcholine increases and REM sleep is initiated.


Histamine is a neurotransmitter that is involved mainly in arousal of the CNS. Neurons in the posterior hypothalamus are active and fire actively when a person is awake, less so when the individual is relaxed or sedate and stop firing altogether during REM and non-REM sleep.


In following, oral supplementation with the proper foods or nutraceuticals can influence the expression of the above neurotransmitters and hormones thus potentially acting as aids in getting a good night’s sleep. We will review these options in the next blog article.

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