ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Modulation of fronto-cortical activity by modafinil: a functional imaging and fos study in the rat.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Modafinil for people with schizophrenia or related disorders.The Cochrane database of systematic reviews · 2019Pooled it
- Neurovascular and synaptic milieu of brain-resident cells in cognitive dysfunction of myalgic encephalomyelitis/chronic fatigue syndrome.Journal of translational medicine · 2026Review
- Modafinil, an atypical CNS stimulant?Advances in pharmacology (San Diego, Calif.) · 2024Article
- Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (Biomolecules · 2020Article
- Article
- phMRI, neurochemical and behavioral responses to psychostimulants distinguishing genetically selected alcohol-preferring from genetically heterogenous rats.Addiction biology · 2019Article
- The effects of single-dose injections of modafinil and methamphetamine on epigenetic and functional markers in the mouse medial prefrontal cortex: potential role of dopamine receptors.Progress in neuro-psychopharmacology & biological psychiatry · 2019Article
- Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination.The international journal of neuropsychopharmacology · 2018Article
- Repeated methamphetamine and modafinil induce differential cognitive effects and specific histone acetylation and DNA methylation profiles in the mouse medial prefrontal cortex.Progress in neuro-psychopharmacology & biological psychiatry · 2018Article
- MAM-E17 rat model impairments on a novel continuous performance task: effects of potential cognitive enhancing drugs.Psychopharmacology · 2017Article
- Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Histamine H3 Receptor Antagonist Prevents Memory Deficits and Synaptic Plasticity Disruption Following Isoflurane Exposure.CNS neuroscience & therapeutics · 2017Article
- Article
- Differential effects of environment-induced changes in body temperature on modafinil's actions against methamphetamine-induced striatal toxicity in mice.Neurotoxicity research · 2015Article
- Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice.Neuropharmacology · 2014Article
- Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.The international journal of neuropsychopharmacology · 2014Article
- The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders.Psychopharmacology · 2013Review
- Differential effect of orexin-1 and CRF-1 antagonism on stress circuits: a fMRI study in the rat with the pharmacological stressor Yohimbine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Article
- Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction.NeuroImage · 2013Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modafinil (MOD) is a wake-promoting drug with pro-cognitive properties. Despite its increasing use, the neuronal substrates of MOD action remain elusive. In particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of MOD action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. Moreover, most animal studies have employed doses of MOD of limited clinical relevance. We used pharmacological magnetic resonance imaging (phMRI) in the anesthetized rat to map the circuitry activated by a MOD dose producing clinically relevant plasma exposure, as here ascertained by pharmacokinetic measurements. We observed prominent and sustained activation of the prefrontal and cingulate cortex, together with weaker but significant activation of the somatosensory cortex, medial thalamic domains, hippocampus, ventral striatum and dorsal raphe. Correlation analysis of phMRI data highlighted enhanced connectivity within a neural network including dopamine projections from the ventral tegmental area to the nucleus accumbens. The pro-arousing effect of MOD was assessed using electroencephalographic recording under anesthetic conditions comparable to those used for phMRI, together with the corresponding Fos immunoreactivity distribution. MOD produced electroencephalogram desynchronization, resulting in reduced delta and increased theta frequency bands, and a pattern of Fos induction largely consistent with the phMRI study. Altogether, these findings show that clinically relevant MOD doses can robustly activate fronto-cortical areas involved in higher cognitive functions and a network of pro-arousing areas, which provide a plausible substrate for the wake-promoting and pro-cognitive effects of the drug.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.