Abstract
Sleep is a neurophysiological state characterized by a gradual decrease in consciousness and alertness in organisms. It is essential for the optimal development of human and other animal species.
In turn, Acetylcholine participates as a neuromodulator for sleep regulation, synaptic transmission and neuronal plasticity through the activation of muscarinic Acetylcholine receptors. Furthermore, sleep disturbances are a common feature across a wide range of mental disorders, including schizophrenia, depression and substance abuse.
Increasing evidence suggests that the cholinergic system, particularly muscarinic Acetylcholine receptors, plays a central role in regulating sleep architecture, cognition, and emotional processes. This review examines the participation of muscarinic Acetylcholine receptors (M1–M5) in the regulation of sleep and in the pathophysiology of mental disorders, and evaluates their potential as therapeutic targets. Current findings indicate that these receptors are differentially involved in modulating cognitive, emotional, and behavioral functions. In particular, the muscarinic Acetylcholine receptors M1 and M4 subtypes are closely associated with sleep and dopaminergic regulation and have demonstrated therapeutic potential in conditions such as schizophrenia and substance use disorders. The muscarinic Acetylcholine receptor-M2 appears to be involved in the generation of REM sleep and affective regulation in depressive states, while muscarinic Acetylcholine receptors-M3 and M5 contribute more indirectly to neural modulation and system-wide balance. Across disorders, alterations in muscarinic signaling are consistently linked to disruptions in sleep architecture, synaptic plasticity, and neural network stability. Overall, muscarinic Acetylcholine receptors represent a promising target for the development of more precise and integrative therapeutic strategies in psychiatry. However, further research is needed to improve pharmacological selectivity and to clarify their clinical applicability.