Background
Modafinil is prescribed for the treatment of narcolepsy. It has been postulated that
modafinil might treat cognitive disruption in neuropsychiatric disorders. The mechanisms
underlying such modafinil-induced improvements in performance have yet to be delineated
however. Recent evidence suggests that modafinil might block the dopamine transporter
(DAT) and that the dopamine D1 receptor (D1R) might contribute to modafinil effects.
Methods
Dopamine D1R wildtype (WT), heterozygous (HT), and knockout (KO) mice received vehicle,
modafinil, or the selective DAT blocker GBR12909 in a progressive ratio breakpoint study.
Results
Both modafinil and GBR12909 increased motivation in the task as measured by an increase in breakpoint in WT and
HT mice. These drug-induced increases in motivation were reduced in dopamine D1R HT
mice relative to their WT littermates. The D1R KO mice did not respond in the task.
Conclusions
These data support the hypothesis that modafinil increases motivation. Moreover, given
the similarity of effects with GBR12909, the data corroborate evidence that the behavioral effects of modafinil might be
due to DAT inhibition. Furthermore, the dopamine D1R might play a downstream role
in mediating modafinil-induced increases in motivation. Thus, studies reporting cognition-enhancing
effects of modafinil might have been influenced by its ability to increase motivation.
Key Words
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Article Info
Publication History
Published online: February 05, 2010
Accepted:
December 18,
2009
Received in revised form:
December 17,
2009
Received:
October 12,
2009
Identification
Copyright
© 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
