Brief ReportAction of Modafinil—Increased Motivation Via the Dopamine Transporter Inhibition and D1 Receptors?
Section snippets
Animals
Dopamine D1R mice, from Jackson Laboratory (Bar Harbor, Maine), were backcrossed for 12 generations onto a C57BL/6J background. Male and female mice WT (n = 8), HT (n = 8), and KO (n = 5) were derived from heterozygous breeding pairs and genotyped. Procedures were approved by the University of California San Diego Institutional Animal Care and Use Committee.
Training and Testing
Training and testing took place in five-hole-operant-chambers (25 × 25 × 25 cm; Med Associates, St. Albans, Vermont). Mice were shaped to
Training
Results are detailed in Supplement 1. The WT and HT mice readily trained to an FR1 and did not differ in total responses [F(1,130) < 1], whereas KO mice did not respond to an FR1, consistent with previous reports (12), and therefore experimental challenge results were compared only between WT and HT mice. No effects of gender or drug × gender interactions were found (p > .1).
Experiment 1: Modafinil Effects on Motivation and Speed of Performance
Main effects of drug [F(3,45) = 4.3, p < .05] and gene [F(1,15) = 5.2, p < .05] and a trend toward a drug × gene
Discussion
Modafinil increased motivation and sped the performance of dopamine D1R WT and HT mice in a PRBS. The effects of modafinil were consistent with those of the selective DAT inhibitor GBR12909. The drug × gene interactions observed for these two compounds suggest that the drug-induced increases in motivation were more robust in WT compared with HT mice. No effect was observed in D1R KO mice, due to their lack of operant responding for reward. The data indicate several important aspects regarding
References (20)
- et al.
Dopaminergic-adrenergic interactions in the wake promoting mechanism of modafinil
Neuroscience
(2005) - et al.
Dopamine in the orbitofrontal cortex regulates operant responding under a progressive ratio of reinforcement in rats
Neurosci Lett
(2004) - et al.
Spatial learning deficit in dopamine D(1) receptor knockout mice
Eur J Pharmacol
(1999) - et al.
Modafinil: A review of neurochemical actions and effects on cognition
Neuropsychopharmacology
(2008) - et al.
Modafinil-induced psychosis
Intern Med J
(2008) - et al.
Modafinil binds to the dopamine uptake carrier site with low affinity
Sleep
(1994) - et al.
Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro
J Pharmacol Exp Ther
(2006) - et al.
Effects of modafinil on dopamine and dopamine transporters in the male human brain: Clinical implications
JAMA
(2009) - et al.
Dopaminergic role in stimulant-induced wakefulness
J Neurosci
(2001) - et al.
Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil
J Neurosci
(2008)