Dopaminergic-Adrenergic Interactions in The Wake Promoting Mechanism of Modafinil

Tomas Thorne

Basic

Last Updated: February 20, 2023

Modafinil Dopamine

Research Based

ResearchPeptides.org follows the strictest sourcing guidelines in the health and nootropics industry. Our focus is to exclusively link to peer-reviewed studies found on respected websites, like PubMed. We focus on finding the most accurate information from the scientific source.

Our goal is to provide you with the most scientifically accurate, unbiased, and comprehensive information regarding all research peptides and SARMs.

All of our content is written by people with a strong science background, including medical researchers.

Our content is continually monitored by an internal peer-review process to ensure accuracy. We strive to never have a piece of inaccurate information on this website.

If you feel that any of our content is inaccurate or out-of-date, please contact us at: [email protected]

ABSTRACT

Adrenergic signaling regulates the timing of sleep states and sleep state-dependent changes in muscle tone. Recent studies indicate a possible role for noradrenergic transmission in the wake-promoting action of modafinil, a widely used agent for the treatment of excessive sleepiness. We now report that noradrenergic projections from the locus coeruleus to the forebrain are not necessary for the wake-promoting action of modafinil. The efficacy of modafinil was maintained after treatment of C57BL/6 mice with N-(2-chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4), which eliminates all noradrenaline transporter-bearing forebrain noradrenergic projections. However, the necessity for adrenergic receptors in the wake-promoting action of modafinil was demonstrated by the observation that the adrenergic antagonist terazosin suppressed the response to modafinil in DSP-4 treated mice. The wake-promoting efficacy of modafinil was also blunted by the dopamine autoreceptor agonist quinpirole. These findings implicate non-noradrenergic, dopamine-dependent adrenergic signaling in the wake-promoting mechanism of modafinil. The anatomical specificity of these dopaminergic-adrenergic interactions, which are present in forebrain areas that regulate sleep timing but not in brain stem areas that regulate sleep state-dependent changes in muscle tone, may explain why modafinil effectively treats excessive daytime sleepiness in narcolepsy but fails to prevent the loss of muscle tone that occurs in narcoleptic patients during cataplexy.

References

Table of Contents
    Add a header to begin generating the table of contents