The effect of CNS drugs and substances on neurotransmission of REM sleep

Abstract

Sleep is a carefully orchestrated state where the individual processes have a specific sequence and duration. The induction and maintenance of wakefulness and sleep are mediated by the combined action of neurotransmitters in strict spatial and temporal contexts. A pharmacological intervention induces neurochemical changes in the brain - intervening in the local neurotransmission mechanisms, disrupting also sleep physiology. In this narrative review, we aimed to focus on the effect of specific Central Nervous System (CNS) drugs and substances on neurotransmission of sleep, particularly Rapid Eye Movement (REM) stage. Most Antidepressants [Selective Serotonin Reuptake Inhibitors (SSRI's), Selective Serotonin Norepinephrine Inhibitors (SNRI's] and histamine agonists maintain the wake - promoting effect of serotonin, epinephrine and histamine, inhibit REM sleep and induce or exacerbate REM Behavior Disorder (RBD). Additionally, orexin modulates sleep by suppressing REM sleep, while orexin - antagonist factors have demonstrated REM - enhancing effects. Gamma-Aminobutyric Acid (GABA) agonists, like benzodiazepines (and alcohol, when its action on GABA), seem to exhibit a sedative role, by increasing muscle atonia in REM sleep. However, results are mixed due to the antagonizing effects of GABAA, GABAB, GABAC receptors based on their relevant anatomic region. Dopaminergic (DA) neurotransmission faces indirectly similar challenges with the antagonizing effects of D1 - like and D2 - like receptors, as shown in DA - dominant conditions like Parkinson's disease, RLS and when antipsychotic drugs are used. AchE inhibitors used in Alzheimer's and other Dementias increase acetylcholine, which has a stimulating effect on wake - ON and REM - ON neurons, and thus benefiting the quality and quantity of REM sleep. REM sleep has a rather complex neurochemical physiology, which can be disorganized by a relevant pharmacologic intervention. As it is an essential component for CNS well-functioning, clinicians' suspicion on adverse effects of CNS drugs on sleep is recommended. © 2022 Nova Science Publishers, Inc.