The Abuse Potential of Modafinil

Mouse study finds that serotonin deficiency does increase depression risk
Mouse study finds that serotonin deficiency does increase depression risk
In order clarify the abuse potential of modafinil, investigators characterized its psychostimulant profile by using mice.

The preclinical and clinical evidence indicates that modafinil, a novel psychostimulant that promotes wakefulness, may diminish persistent fatigue and sleepiness in individuals who were diagnosed with major depressive disorder (MDD). Modafinil also shows promise as an augmenter of antidepressant medications in patients who continue to experience residual tiredness or fatigue.

To date, inconsistent results have been reported with regard to the abuse potential of modafinil. Because of the recent increase in use of modafinil among students and professionals, “a better understanding of the behavioral actions and related neurochemistry of modafinil is necessary to monitor its potential for abuse alone and in combination with illicit psychostimulants,” wrote the authors of a study that was recently published by European Journal of Neuroscience.

Researchers affiliated with the National Institute on Drug Abuse (NIDA) and The University of Kansas used mice to assess the neurochemical and behavioral actions of modafinil in order to help clarify its abuse potential.

They used in-vivo brain microdialysis to determine dopamine (DA) values in the brains of mice treated with modafinil, and they used a cocaine discrimination task, in which mice are trained to discriminate cocaine from saline when cocaine is administered alone or concomitantly with modafinil, to examine the cocaine-like subjective effect of modafinil. 

Following intraperitoneal administration of modafinil, researchers observed a significant, dose-dependent increase of extracellular DA in both the nucleus accumbens shell (NAS) and core (NAC). Modafinil administration also enhanced cocaine effects when these two drugs were co-administered. “The potency of cocaine in combination with 30 mg/kg of modafinil was more than 10-fold greater than that for cocaine alone,” the authors noted.

“Although inhibition of DA reuptake may be a primary mechanism underlying modafinil’s therapeutic actions, non DA-dependent actions [ie, changes in the levels of glutamate or orexin] may be playing a role in its psychostimulant profile,” they concluded.

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Mereu M, Chun LE, Prisinzano T, et al. The unique psychostimulant profile of (±)-Modafinil: investigation of behavioral and neurochemical effect in mice. Eur J Neurosci. 2016. doi: 10.1111/ejn.13376. (Epub ahead of print]