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Benzodiazepines are a family of molecules, some of which are used as sleep-inducing medications, while others are used as tranquilizers.
Benzodiazepines bind to a specific site on a neuron’s receptor for GABA, a neurotransmitter that counteracts the brain’s wakefulness mechanisms. Thus benzodiazepines promote sleep by augmenting this natural process.
The same gabaergic receptor also has binding sites that can be used both by barbiturates (a class of drugs once commonly used as sleep aids but now almost never used for that purpose) and by anesthetics, whose purpose is to put surgical patients to sleep.
Molecules that build up and make you sleep
As each day draws to a close, you feel the need to lie down and go to sleep. The onset of sleep, which seems like such a simple phenomenon from a behavioral perspective, is actually quite complex from a molecular one.
In the early 20th century, French psychologist Henri piéron hypothesized that prolonged wakefulness causes the build-up of a “sleep toxin" that is subsequently broken down during sleep. To test his hypothesis, piéron walked dogs through Paris at night to prevent them from sleeping. He then injected their cerebrospinal fluid into the brains of other dogs. He found that these other dogs then slept longer and more deeply than usual.
We now know that the “hypnogenic” (sleep-inducing) substances that piéron hypothesized do in fact exist. Some of them are small protein molecules that are produced by brain structures such as the hypothalamus and that inhibit the neurons of the wakefulness system.
But these proteins are not the only hypnogenic molecules. The build-up of serotonin in certain parts of the brain during periods of wakefulness also contributes to the onset of sleep. The serotonin level in certain areas of the brain also affects mood. That is why some problems such as depression and anxiety often lead to sleep disorders. People with low serotonin levels also tend to spend less time in restorative non-rem sleep over the course of the night.
Serotonin also plays an important role in sleep because the body uses it to synthesize melatonin. Melatonin is produced at night and plays a fundamental role in regulating the body’s biological clock. In fact, melatonin governs the entire sleep/wake cycle, whereas serotonin is involved more specifically in wakefulness, in triggering sleep, and in rem sleep.
Diagram of a melatonin molecule-
(atoms: pale blue = carbon, dark blue = nitrogen, red = oxygen,
White = hydrogen)
Thus sleep is triggered by two inter-related processes: the production and build-up of hypnogenic substances in the body while we are awake, and cyclical fluctuations in substances such as melatonin that are associated with our body’s biological clock.
Among the hypnogenic substances that build up while we are awake, adenosine has been the subject of much discussion since the mid-1990s.