Many people know the feeling of heavy eyelids and eyes closing on their own. Scientists have long searched for the mechanism that signals the brain that it's time to sleep. New research by Chinese scientists suggests that a little-studied molecule called tryptamine may play a key role in this process, reports infohub.kz.
The findings were published in the journal Nature Neuroscience. The researchers studied the so-called homeostatic sleep pressure—the process where the urge to sleep increases with time spent awake. Experiments were conducted on nocturnal animals (mice) and diurnal animals (pigs).
Previously, adenosine was thought to be the main chemical signal for this process, but it could not fully explain how the brain knows it's time to sleep. In the new study, scientists identified another potential player: tryptamine. This substance was previously considered a little-known neuromodulator with an unknown physiological role.
Experiments showed that tryptamine levels gradually rise during wakefulness: the longer animals stayed awake, the higher its concentration in the cerebrospinal fluid. Further investigation revealed that tryptamine activates the GPR139 receptor located in the preoptic area of the hypothalamus, a key sleep regulation center. Activation of this receptor strengthened the activity of neurons responsible for transitioning to sleep.
When scientists blocked tryptamine synthesis or disabled the GPR139 receptor, animals recovered sleep significantly worse after a period of forced wakefulness, and the natural mechanism for compensating for sleep loss was disrupted. Conversely, drugs that activate GPR139 increased sleep duration and improved sleep quality in both species.
The authors believe that tryptamine could become a new target for developing insomnia medications. Many existing sleep aids affect the nervous system broadly and cause side effects or dependence. The new approach could potentially target the natural mechanism by which the brain itself determines that the body needs sleep.
However, it is too early to apply the discovery in clinical practice: all major experiments were conducted on mice and pigs. The study did not include humans and does not prove that drugs targeting the GPR139 receptor would be safe and effective. The authors emphasize that tryptamine is likely not the only molecule regulating sleep—it may work together with other substances, including adenosine, forming a complex sleep control system. The next step should involve human studies and clinical trials of potential drugs.