Wake-promoting agent modafinil worsened attentional performance following REM sleep deprivation in a young-adult rat model of 5-choice serial reaction time task

Liu, Yia Ping; Tung, Che Se; Lin, Yu Wen; Chuang, Chia Hsin

doi:10.1007/s00213-010-2019-0

Cited by 13 publications

(6 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An impairing effect of 40 mg/kg modafinil on d’ in the Df(h22q11)/+ model is similar to the observed higher-dose effects (64 mg/kg) on the rCPT in the MAM-E17 rat model of schizophrenia 31 . It is also consistent with the higher-dose effects of modafinil (64–100 mg/kg) observed in other tests of attention and/or inhibitory control, including decreased accuracy 73 and increased premature responding in the 5-CSRTT 73 , 74 and impaired Go-accuracy in the stop-signal reaction time task 43 . Low-to-moderate doses of modafinil have nevertheless been shown to improve stop-signal reaction time (10 mg/kg 43 ) and CPT d’ in healthy rats (8 mg/kg) 31 and fronto-striatal dependent cognition, including attention, in humans (100–200mg 75 – 77 ).…”

Section: Discussionsupporting

confidence: 87%

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

et al. 2018

View full text Add to dashboard Cite

The 22q11.2 deletion syndrome (22q11.2DS) confers high risk of neurodevelopmental disorders such as schizophrenia and attention-deficit hyperactivity disorder. These disorders are associated with attentional impairment, the remediation of which is important for successful therapeutic intervention. We assessed a 22q11.2DS mouse model (Df(h22q11)/+) on a touchscreen rodent continuous performance test (rCPT) of attention and executive function that is analogous to human CPT procedures. Relative to wild-type littermates, Df(h22q11)/+ male mice showed impaired attentional performance as shown by decreased correct response ratio (hit rate) and a reduced ability to discriminate target stimuli from non-target stimuli (discrimination sensitivity, or d’). The Df(h22q11)/+ model exhibited decreased prefrontal cortical-hippocampal oscillatory synchrony within multiple frequency ranges during quiet wakefulness, which may represent a biomarker of cognitive dysfunction. The stimulant amphetamine (0–1.0 mg/kg, i.p.) dose-dependently improved d’ in Df(h22q11)/+ mice whereas the highest dose of modafinil (40 mg/kg, i.p.) exacerbated their d’ impairment. This is the first report to directly implicate attentional impairment in a 22q11.2DS mouse model, mirroring a key endophenotype of the human disorder. The capacity of the rCPT to detect performance impairments in the 22q11.2DS mouse model, and improvement following psychostimulant-treatment, highlights the utility and translational potential of the Df(h22q11)/+ model and this automated behavioral procedure.

show abstract

Section: Discussionsupporting

confidence: 87%

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Modafinil has shown mixed effects for cognitive enhancements in healthy human subjects but generally improves performance on tests of sustained and focused attention at more difficult task parameters using low to moderate doses (Scoriels et al 2013 ; Battleday and Brem 2015 ). While the majority of studies using young, healthy rodents in the 5-CSRTT has found either no effect or reductions in attentional accuracy and/or inhibitory control (Milstein et al 2003 ; Waters et al 2005 ; Liu et al 2010 ), such results may be explained by the use of higher dose ranges (>30 mg/kg) and/or insufficient task difficulty. We also found that higher doses of modafinil in the rCPT increased FAR and ISI touches, decreased criterion ( c ), and a significant linear trend toward faster correct response latencies across all animals.…”

Section: Discussionmentioning

confidence: 99%

MAM-E17 rat model impairments on a novel continuous performance task: effects of potential cognitive enhancing drugs

et al. 2017

View full text Add to dashboard Cite

RationaleImpairments in attention and inhibitory control are endophenotypic markers of neuropsychiatric disorders such as schizophrenia and represent key targets for therapeutic management. Robust preclinical models and assays sensitive to clinically relevant treatments are crucial for improving cognitive enhancement strategies.ObjectivesWe assessed a rodent model with neural and behavioral features relevant to schizophrenia (gestational day 17 methylazoxymethanol acetate treatment (MAM-E17)) on a novel test of attention and executive function, and examined the impact of putative nootropic drugs.MethodsMAM-E17 and sham control rats were trained on a novel touchscreen-based rodent continuous performance test (rCPT) designed to closely mimic the human CPT paradigm. Performance following acute, systemic treatment with an array of pharmacological compounds was investigated.ResultsTwo cohorts of MAM-E17 rats were impaired on rCPT performance including deficits in sensitivity (d′) and increased false alarm rates (FARs). Sulpiride (0–30 mg/kg) dose-dependently reduced elevated FAR in MAM-E17 rats whereas low-dose modafinil (8 mg/kg) only improved d′ in sham controls. ABT-594 (5.9–19.4 μg/kg) and modafinil (64 mg/kg) showed expected stimulant-like effects, while LSN2463359 (5 mg/kg), RO493858 (10 mg/kg), atomoxetine (0.3–1 mg/kg), and sulpiride (30 mg/kg) showed expected suppressant effects on performance across all animals. Donepezil (0.1–1 mg/kg) showed near-significant enhancements in d′, and EVP-6124 (0.3–3 mg/kg) exerted no effects in the rCPT paradigm.ConclusionThe MAM-E17 model exhibits robust and replicable impairments in rCPT performance that resemble attention and inhibitory control deficits seen in schizophrenia. Pharmacological profiles were highly consistent with known drug effects on cognition in preclinical and clinical studies. The rCPT is a sensitive and reliable tool with high translational potential for understanding the etiology and treatment of disorders affecting attention and executive dysfunction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-017-4679-5) contains supplementary material, which is available to authorized users.

show abstract

“…Also, scopolamine-induced impairment of 5-CSRTT performance could not be reversed by Modafinil treatment. Dopaminergic effects are mainly related to speed and probability of responding ( Baunez and Robbins, 1999 ; Milstein et al, 2003 ), whereas improvement of accuracy could be observed mainly in rodents with low baseline performance ( Granon et al, 2000 ). Modafinil has sympathomimetic effects and can directly influence the locus coeruleus activity, the main source of noradrenaline in the brain, via activation of hypocretin ( Ivanov and Aston-Jones, 2000 ; Chudasama and Robbins, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats

Nikiforuk

Kalaba

Ilić

et al. 2017

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Reduced cognitive abilities are often characterized by an impairment of flexibility, i.e., the ability to switch from learned rules or categories that were important in certain contexts to different new modalities that rule the task. Drugs targeting the dopamine transporter (DAT) are widely used for their potential to enhance cognitive abilities. However, commercially available drugs are of limited specificity for DAT, blocking also noradrenaline and serotonine transporters, that can lead to unwanted side effects in healthy subjects. Therefore, we tested a newly synthetized compound (CE-123) with higher specificity for DAT in male rats in an attentional set-shifting task (ASST), that proves for cognitive flexibility and a 5-choice serial-reaction time task (5-CSRTT) assessing visuospatial attention and impulsivity. Treated rats at a dose of 0.3 and 1.0 but not 0.1 mg/kg bodyweight showed reduced extra-dimensional shifts in the ASST compared to controls indicating increased cognitive flexibility. Rats treated with R-Modafinil, a commercially available DAT inhibitor at a dose of 10 mg/kg bodyweight showed increased premature responses, an indicator of increased impulsivity, during a 10 s but not a 2.5, 5, or 7.5 s intertrial interval when compared to vehicle-treated rats in the 5-CSRTT. This was not found in rats treated with CE-123 at the same dose as for R-Modafinil. Visuospatial attention, except premature responses, did not differ between R-Modafinil and CE-123-treated rats and their respective controls. Thus, CE-123 increased cognitive flexibility with diminished impulsivity.

show abstract

Wake-promoting agent modafinil worsened attentional performance following REM sleep deprivation in a young-adult rat model of 5-choice serial reaction time task

Abstract: These results suggest that aging might be a crucial factor for the physiological impact following REMD. MOD should be used cautiously, particularly, in conditions that require REM sleep.

Cited by 13 publications

References 63 publications

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine

MAM-E17 rat model impairments on a novel continuous performance task: effects of potential cognitive enhancing drugs

A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats

Contact Info

Product

Resources

About