Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine

Engber, Thomas M.; Dennis, Shelley A; Jones, Barry D.; Miller, Matthew S.; Contreras, Patricia C.

doi:10.1016/s0306-4522(98)00015-3

Cited by 90 publications

(48 citation statements)

References 25 publications

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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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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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“…These compounds affect dopaminergic (DA) and noradrenergic systems, which are mainly involved in the control of locomotor activity (Anden et al 1973). Modafinil does not modulate the DA system, as modafinil lacks pronounced effects on motor function areas (Engber et al 1998;Lin et al 1996). Indeed, the dopamine D 2 receptor antagonists haloperidol and sulpiride did not prevent the modafinil-induced locomotor activity (Duteil et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The doses chosen were based on earlier studies in marmosets, rats, and mice (Jenner et al 2000;Engber et al 1998;Duteil et al 1990). The peak activity of modafinil in marmoset monkeys was 2 h after administration with effects lasting more than a 10-h period (Jenner et al 2000).…”

Section: Methodsmentioning

confidence: 99%

“…The morphological distribution of neural active areas after modafinil implicates involvement in sleep-wake regulation, like the anterior hypothalamic nucleus and adjacent areas, but not in motor function areas (Engber et al 1998;Lin et al 1996;Scammell et al 2000). Modafinil modulates neurotransmitter function, such as noradrenaline (NA) indirectly, as modafinil-induced locomotor activity is prevented by an α 1 -adrenoreceptor antagonist (Duteil et al 1990).…”

Section: Introductionmentioning

confidence: 99%

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Behavioral effects of modafinil in marmoset monkeys

et al. 2006

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Rationale: Modafinil is increasingly used in sleep disturbances in general and in neurodegenerative diseases and is recently being used in healthy people for attention control. However, the application of modafinil is possibly not only restricted to alertness enhancing effects. More insight in this compound may lead to new applications. Not all behavioral aspects have been studied sufficiently; therefore, more detailed investigations on modafinil's positive and aversive behavioral effects are addressed in this paper. Objectives: Determination of effects of modafinil in marmoset monkeys with observational methods and with behavioral tests measuring locomotor activity, hand-eye coordination, response to a threat situation and startle response. Materials and methods: Two hours after oral administration of modafinil in doses of 50, 100, 150, and 225 mg/kg, animals were observed and tested in the behavioral test systems. Results: Locomotor activity was increased after 100 mg/ kg modafinil in the Bungalow test and after 100, 150, and 225 mg/kg, as found in the movement parameters of the human threat test. Moreover, modafinil showed anxiolyticlike effects in the human threat test. No other side effects were observed, nor were the hand-eye coordination and startle response affected. Conclusions: Besides psychostimulation, modafinil has no aversive effects in the doses used in the domains measured. The potential anxiolyticlike effects of modafinil may create new possibilities for the therapeutic use of modafinil.

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“…Estos efectos son mediados por los receptores dopaminérgicos. El metilfenidato bloquea estos receptores en distintas áreas cerebrales y el modafinilo actúa inhibiendo los transportadores de dopamina en áreas cerebrales específicas que regulan el ritmo sueño-vigilia [23][24] . Las indicaciones aprobadas para metilfenidato son déficit de atención e hiperactividad en niños y adolescentes y narcolepsia, y las del modafinilo, somnolencia diurna en pacientes con narcolepsia, trastornos del sueño por turnos de trabajo y apnea obstructiva del sueño con somnolencia excesiva residual a pesar del uso óptimo de presión positiva continua.…”

Section: Uso De Psicoestimulantes En El Tratamiento De La Astenia En unclassified

Astenia en cáncer avanzado y uso de psicoestimulantes

Tejedor

Rubiales

Martínez

et al. 2011

Anales Sis San Navarra

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Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine

Cited by 90 publications

References 25 publications

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

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

Behavioral effects of modafinil in marmoset monkeys

Astenia en cáncer avanzado y uso de psicoestimulantes

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