Differential patterns of regional c-Fos induction in the rat brain by amphetamine and the novel wakefulness-promoting agent modafinil

Engber, Thomas M.; Koury, Elizabeth J.; Dennis, Shelley A; Miller, Matthew S.; Contreras, Patricia C.; Bhat, Ratan V.

doi:10.1016/s0304-3940(97)00962-2

Cited by 111 publications

(83 citation statements)

References 18 publications

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“…Hypoglycaemia and agents that close the beta cell K-ATP channel both stimulate neuronal GABA, at least in some brain regions, providing indirect evidence for the above hypothesis [15]. Modafinil, like the state of hypoglycaemia, has been shown to enhance c-fos immunoreactivity within the hypothalamus [38]. At the dose used in our study, modafinil had no effect on any of the counter-regulatory hormones measured, but did increase the heart rate and enhance autonomic symptom response to hypoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia

et al. 2004

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Aims/hypothesis. Our hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia. Methods. Nine healthy men received, in random order, two 100-mg doses of modafinil or placebo, followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia (four studies). Catecholamines, symptom scores and cognitive function were measured. Results. Modafinil had no effect on the measured parameters during euglycaemia. During hypoglycaemia, autonomic symptom scores were significantly higher with modafinil (increase at lowest plasma glucose concentration 271.3±118.9 vs 211.2±80.4/40 min, p=0.019), and the heart rate response was increased (12,928±184 vs 6773±148 bpm/140 min, p=0.016). Deterioration in performance of two cognitive tasks was reduced: Stroop colour-word test (613±204 vs 2375±161/65 min, p=0.009) and accuracy of a simple reaction task (11.3±1.8 vs 9.4±3.7, p=0.039). Conclusions/interpretation. We conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia, possibly by reducing neuronal central GABA concentrations.

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Section: Discussionmentioning

confidence: 99%

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia

et al. 2004

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“…Concerning the effects of modafinil on Fos labelling in brain, modafinil induced marked Fos staining in anterior hypothalamus on cat . Moreover, Engber et al (1998) found by c-Fos immunohistochemistry that the neural targets for modafinil not only include anterior hypothalamus, but also amygdala. These results are consistent with our present work, where Fos staining was previously decreased in anterior hypothalamus and amygdala after sleep deprivation and cognitive task, and then restored by modafinil.…”

Section: Paraventricular Nucleus)mentioning

confidence: 98%

“…Concerning the neuroanatomical brain targets of modafinil, some authors observed that c-Fos protein expression increased in the anterior hypothalamus following modafinil administration (Lin et al, 1996 ;Engber et al, 1998) and orexin-containing neurons (Scammel et al, 2000). Neither one of these studies, however, was performed after a sleep deprivation period followed by cognitive tasks; hence the brain targets of modafinil remain a matter for debate (Gallopin et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice

Piérard

Liscia

Philippin

et al. 2007

Pharmacology Biochemistry and Behavior

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Abstract:The original aims of our study have been to investigate in sleep-deprived mice, the effects of modafinil administration on spatial working memory, in parallel with the evaluation of neural activity level, as compared to non sleep-deprived animals. For this purpose, an original sleepdeprivation apparatus was developed and validated with continuous electroencephalography recording. Memory performance was evaluated using spontaneous alternation in a T-maze, whereas the neural activity level was estimated by the quantification of the c-Fos protein in various cerebral zones. This study allowed altogether:First, to evidence that a diurnal 10-hr sleep deprivation period induced an impairment of spatial working memory.Second, to observe a decrease in c-Fos expression after sleep deprivation followed by a behavioural test, as compared to non sleep-deprived mice. This impairment in neural activity was evidenced in areas involved in wake-sleep cycle regulation (anterior hypothalamus and supraoptic nucleus), but also in memory (frontal cortex and hippocampus) and emotions (amygdala).Finally, to demonstrate that modafinil 64 mg/kg is able to restore on the one hand memory performance after a 10-hr sleep deprivation period, and on the other hand, the neural activity level in the very same brain areas where it was previously impaired by sleep deprivation and cognitive task.

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“…injection of modafinil has diminished effect in comparison to its equivalent amphetamine concentration administrated i.v (Engber et al, 1998a;Florence et al, 2000). In addition the effect of the anaesthesia alters modafinil pharmacokinetics (Florence et al, 2000), unlike the freely-behaving animals (Engber et al, 1998a;Engber et al, 1998b). Therefore the target of our bolus dose of modafinil was to overcome the decreased drug distribution of i.p.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus

Tsanov¹,

Lyons²,

Barlow³

et al. 2010

Neuropharmacology

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, S.M. The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus, Neuropharmacology (2010Neuropharmacology ( ), doi: 10.1016Neuropharmacology ( /j.neuropharm.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTThe psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT AbstractModafinil is a psychostimulant drug used widely for the treatment of narcolepsy, which also has additional positive effects on cognition. Here, we investigate the effects of modafinil on behavioral performance and synaptic plasticity in rats.Improved acquisition of water maze task was observed for animals that underwent chronic treatment with modafinil. We found that the distance travelled and escape latency were reduced after the first day in chronically-treated rats, compared to controls. Importantly, the swim velocity was similar for both groups, excluding pharmacological effects on motor skills. We also found that modafinil increases synaptic plasticity in the dentate gyrus of urethane-anaesthetized rats; modafinil induced a robust augmentation of the population spike, evident after application of 2 bursts of 200Hz, high-frequency stimulation. Furthermore, the modafinil-dependent enhancement of postsynaptic potentials correlated selectively with theta rhythm augmentation. We propose that modafinil may facilitate spatial orientation via increased theta-related hippocampal plasticity.

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Differential patterns of regional c-Fos induction in the rat brain by amphetamine and the novel wakefulness-promoting agent modafinil

Cited by 111 publications

References 18 publications

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia

Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice

The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus

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