The role of the locus coeruleus-norepinephrine system in the regulation of arousal states during sleep and wakefulness

Summary description of the study

The brain's arousal state is regulated by various neurotransmitter systems, particularly the noradrenergic locus coeruleus (LC) in the brainstem. The activity of the locus coeruleus and the resulting arousal state influence essential cognitive functions such as attention and memory, and are crucial for our well-being. High arousal levels have been associated with anxiety, sleep, and stress-related disorders. In recent studies, we have shown that individuals can voluntarily influence their arousal state during wakefulness through mental strategies in a pupil-based biofeedback training. Additionally, we have replicated animal studies that demonstrate that the brain's arousal state fluctuates significantly during certain sleep phases and that pupil size provides important insights into sleep phases, sleep continuity, and sleep dynamics. In the following study, we investigate in two experiments the causal role of the locus coeruleus-norepinephrine system in regulating the arousal state during wakefulness and sleep. We plan to explore this relationship by administering clonidine (trade name Catapresan®), a medication that reduces norepinephrine release in the central nervous system. The first experiment will provide insights into whether the voluntary control of arousal state during wakefulness is primarily governed by the norepinephrine system. The second experiment will examine whether the norepinephrine system is responsible for fluctuations in arousal state during different sleep phases. The results of this study are significant for understanding fundamental brain functions and could contribute to the development of non-invasive methods to enhance well-being during wakefulness as well as improve sleep quality.

(BASEC)

Intervention under investigation

In our study, participants are randomly assigned to groups. This is important to obtain reliable results from the study. This is called randomization. Each group receives a different treatment. In our study, there are two groups: • Group 1 (experimental group) receives the study medication clonidine at a dosage of 0.15 mg. • Group 2 (control group) receives a placebo, a vitamin C capsule at a dosage of 100 mg. The study is a so-called double-blind study. “Double-blind” means that no one involved in the conduct of the study knows which group the participants have been assigned to: the participants themselves do not know which group they are in. Even the testing person does not know which group individual participants belong to. In this sense, all participants are “blind.” The idea is to minimize any influence on the results. Through randomization and double-blinding, we can objectively assess how well the study medication clonidine actually works.

(BASEC)

Disease under investigation

In this project, only healthy participants are examined.

(BASEC)

Sponsor

NA

(BASEC)

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Zurich

(BASEC)

Date of authorisation

06.12.2024

(BASEC)

Results of the trial