Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain

Volkow, Nora D.; Fowler, Joanna S.; Logan, Jean; Alexoff, David; Zhu, Wei; Telang, Frank; Wang, Gene‐Jack; Jayne, Millard; Hooker, Jacob M.; Wong, Christopher; Hubbard, Barbara; Carter, Pauline; Warner, D.D.; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog-Torres, Karen

doi:10.1001/jama.2009.351

Cited by 489 publications

(388 citation statements)

References 35 publications

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“…Modafinil has been shown to elevate extracellular levels of dopamine in humans by blocking the dopamine transporter (DAT) (Volkow et al, 2009), and dopamine regulation in both the anterior cingulate and insular cortices by DAT has been demonstrated in humans (Ciliax et al, 1999). Both the ACC and the dopamine-rich striatal areas to which it projects comprise major neural circuitry, which supports the associative learning ability examined in our study (Haber and Knutson, 2010).…”

Section: Discussionsupporting

confidence: 77%

“…This action includes inhibition of catecholamine transporters (Madras et al, 2006;Volkow et al, 2009;Zolkowska et al, 2009), thereby increasing extracellular dopamine and norepinephrine levels. Given the important role of dopamine for associative learning and reward processing (eg, Schultz et al, 1997), and the abnormalities in dopamine markers observed in MA subjects Volkow et al, 2001a;Wilson et al, 1996), modafinil may be particularly well-suited as an agent that promotes enhanced learning via improved dopaminergic function in MA-dependent subjects.…”

Section: Introductionmentioning

confidence: 99%

“…The associative learning task was selected on the basis of prior work showing that it elicits fMRI activation in neural circuitry important for learning (Ghahremani et al, 2010). Moreover, as preliminary findings indicated that performance on this task was worse in MA-dependent individuals than in healthy control subjects, and negatively correlated with dopamine D2/D3 receptor availability (Ghahremani et al, 2009), we expected modafinil to improve performance in MA-dependent individuals, given evidence that it can enhance dopaminergic function (Madras et al, 2006;Volkow et al, 2009). Brain activation related to performing the task was assessed, testing for modafinil's effects and the potential interactions of this effect with the participant group.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

Ghahremani

Tabibnia

Monterosso

et al. 2011

Neuropsychopharmacol

109

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Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function. Therefore, medications that improve cognition in these subjects may improve the success of therapy for their addiction, especially when cognitive behavioral therapies are used. Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers. We therefore conducted a randomized, double-blind, placebo-controlled, cross-over study, using functional magnetic resonance imaging, to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent, MA-dependent, and healthy control participants. Modafinil (200 mg) and placebo were administered orally (one single dose each), in counterbalanced fashion, 2 h before each of two testing sessions. Under placebo conditions, MA-dependent participants showed worse learning performance than control participants. Modafinil boosted learning in MA-dependent participants, bringing them to the same performance level as control subjects; the control group did not show changes in performance with modafinil. After controlling for performance differences, MAdependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants. The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control. These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence. Neuropsychopharmacology (2011) 36, 950-959;

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

Ghahremani

Tabibnia

Monterosso

et al. 2011

Neuropsychopharmacol

109

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“…However, evidence in both animals and humans supports a predominantly dopamine-mediated action. [3][4][5] Further, it shares many of the psychiatric complications and abuse potential of other psychostimulants. 1 • psychostimulants are only initiated by palliative-care specialists and for short-term use; the GP would only take over prescribing where longerterm use is envisaged or where it is in the patient's best interest…”

Section: Mode Of Actionmentioning

confidence: 99%

GP guide to drugs used in palliative care: psychostimulants

Howard¹,

Howard²

2012

Prescriber

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“…Modafinil is one such agent, a lowpotency inhibitor of the plasma membrane transporters for NE and dopamine (NET and DAT, respectively) (Madras et al, 2006;Volkow et al, 2009) that increases NE and DA in the cortex (see (Minzenberg and Carter, 2008a) for review). In an earlier fMRI study, we found that modafinil enhances in healthy subjects cognitive control-related activity in the LC, the distributed cognitive control network, and functional connectivity between the two (Minzenberg et al, 2008b).…”

Section: Introductionmentioning

confidence: 99%

Sustained Modafinil Treatment Effects on Control-Related Gamma Oscillatory Power in Schizophrenia

Minzenberg

Yoon

Cheng

et al. 2015

Neuropsychopharmacol

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Control-related cognitive processes such as rule selection and maintenance are associated with cortical oscillations in the gamma range, and modulated by catecholamine neurotransmission. Control-related gamma power is impaired in schizophrenia, and an understudied treatment target. It remains unknown whether pro-catecholamine pharmacological agents augment control-related gamma oscillations in schizophrenia. We tested the effects of 4-week fixed-dose daily adjunctive modafinil (MOD) 200 mg, in a randomized double-blind, placebo-controlled, parallel-groups design. Twenty-seven stable schizophrenia patients performed a cognitive control task during EEG, at baseline and after 4 weeks of treatment. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-80 Hz oscillations. The modafinil group (n = 14), relative to placebo group (n = 13), exhibited enhanced oscillatory power associated with high-control rule selection in the gamma range after treatment, with additional effects during rule maintenance in gamma and sub-gamma ranges. MOD-treated patients who exhibited improved task performance with treatment also showed greater treatmentrelated delay period gamma compared with MOD-treated patients without improved performance. This is the first evidence in schizophrenia of augmentation of cognition-related gamma oscillations by an FDA-approved agent with therapeutic potential. Gamma oscillations represent a novel treatment target in this disorder, and modulation of catecholamine signaling may represent a viable strategy at this target.

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Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain

Cited by 489 publications

References 35 publications

Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals

GP guide to drugs used in palliative care: psychostimulants

Sustained Modafinil Treatment Effects on Control-Related Gamma Oscillatory Power in Schizophrenia

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