Effects of post-training modafinil administration in a discriminative avoidance task in mice

Fernandes, H.A.; Zanin, Karina A.; Patti, Camilla de Lima; Lopes-Silva, Leonardo B.; Bizerra, C.S.; Bittencourt, Lia; Tufik, Sérgio; Frussa‐Filho, Roberto

doi:10.1017/neu.2015.16

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…There were some trends towards decreased rearing behaviour in the central part of the arena in the prenatally exposed mice but this profile was not shown in all measurements. This is in accordance with a study where modafinil dose range 32, 64 and 128 mg/kg did not alter elevated plus behaviour (Fernandes et al 2015). In clinical studies, only modafinil overdose was shown to be anxiogenic (Spiller et al 2009, Carstairs et al 2010 while clinically relevant dose in healthy volunteers lead to improved mood and no anxiety (Taneja et al 2007).…”

Section: Discussionsupporting

confidence: 90%

Prenatal Exposure to Modafinil Alters Locomotor Behaviour and Leucocyte Phagocytosis in Mice

et al. 2018

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Background: Modafinil is a psychostimulant drug prescribed mainly for treatment of narcolepsy but is used as a "smart drug" by wide populations to increase wakefulness, concentration and overall mental performance. The aim of this study was to assess potential developmental toxicity of modafinil. Materials and methods: Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestational day (GD) 3 to GD 10 and then a challenge dose on the GD 17. The male offspring were treated analogously at the age of 10 weeks. Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open-field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. Results: The most important finding of this study was the immunosuppressing effect on leukocyte activity, hypolocomotion and increased behavioural response to modafinil-induced psychostimulation caused by prenatal exposure to the same drug. We did not detect significantly altered anxiety-related behaviour in any group disregarding the pre-and postnatal treatments. Conclusion: This is the first evidence of developmental toxicity of modafinil which needs to be taken into account as a potential risk factor when modafinil is administered to women who may become or are pregnant.

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Section: Discussionsupporting

confidence: 90%

Prenatal Exposure to Modafinil Alters Locomotor Behaviour and Leucocyte Phagocytosis in Mice

et al. 2018

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“…However, to prevent overstating the importance of our results, it is necessary to note, that in our study the absolute differences in values were very small (albeit significant). Interestingly, there is also a study with an opposite outcome where modafinil dose range 32, 64 and 128 mg/kg did not alter elevated plus behaviour (Fernandes et al, 2015) and also our own data indicate this design may not capture the anxiogenic effect (Ruda‐Kucerova et al, 2017).…”

Section: Discussionmentioning

confidence: 76%

Prenatal exposure to modafinil alters behavioural response to methamphetamine in adult male mice

Pistovčáková

Amchová

Šulcová

et al. 2018

Intl J of Devlp Neuroscience

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Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy. However, it is used as a "smart drug" especially by young adults to increase wakefulness, concentration and mental performance. Therefore, it can also be used by women with childbearing potential and its developmental effects can become a concern. The aim of this study was to assess behavioural and immune effects of prenatal modafinil exposure in mice and to evaluate the reaction to methamphetamine exposure on these animals in adult age. Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestation day (GD) 3 to GD 10 and then a challenge dose on GD 17. The male offspring were treated analogously at the age of 10 weeks with methamphetamine (2.5 mg/kg orally). Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open field test were assessed in naïve animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. The modafinil prenatally exposed mice showed basal hypolocomotion, increased anxiety, lower locomotor effect of acute methamphetamine and increased vulnerability to behavioural sensitization. The leukocyte activity did not show significant differences. Prenatal modafinil exposure alters basal behavioural profile, decreases acute effect of methamphetamine and enhances vulnerability to development of behavioural sensitization at adulthood. This may lead to higher vulnerability to development of addiction.

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Solriamfetol improves chronic sleep fragmentation-induced increases in sleep propensity and ameliorates explicit memory in male mice

Puech

Badran

Barrow

et al. 2023

Sleep

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Obstructive sleep apnea (OSA) is a highly prevalent condition characterized by episodes of partial or complete breath cessation during sleep that induce sleep fragmentation (SF). One of the frequent manifestations of OSA is the presence of excessive daytime sleepiness (EDS) associated with cognitive deficits. Solriamfetol (SOL) and modafinil (MOD) are wake promoting agents commonly prescribed to improve wakefulness in OSA patients with EDS. This study aimed to assess the effects of SOL and MOD in a murine model of OSA characterized by periodic SF. Male C57Bl/6J mice were exposed to either control sleep (SC) or SF (mimicking OSA) during the light period (06:00h to 18:00h) for 4 weeks, which consistently induces sustained excessive sleepiness (ES) during the dark phase. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200mg/kg), MOD (200mg/kg) or vehicle (VEH) for 1 week while continuing exposures to SF or SC. Sleep/wake activity and sleep propensity were assessed during the dark phase. Novel object recognition (NOR), elevated-plus maze test (EPMT), and forced swim test (FST) were performed before and after treatment. SOL or MOD decreased sleep propensity in SF, but only SOL induced improvements in explicit memory, while MOD exhibited increased anxiety behaviors. Chronic SF, a major hallmark of OSA, induces EDS in young adult mice that is mitigated by both SOL and MOD. SOL, but not MOD, significantly improves SF-induced cognitive deficits. Increased anxiety behaviors are apparent in MOD treated mice. Further studies aiming to elucidate the beneficial cognitive effects of SOL are warranted.

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Effects of post-training modafinil administration in a discriminative avoidance task in mice

Abstract: Modafinil impaired memory consolidation in a dose- and time-dependent fashion.

Cited by 3 publications

References 28 publications

Prenatal Exposure to Modafinil Alters Locomotor Behaviour and Leucocyte Phagocytosis in Mice

Prenatal Exposure to Modafinil Alters Locomotor Behaviour and Leucocyte Phagocytosis in Mice

Prenatal exposure to modafinil alters behavioural response to methamphetamine in adult male mice

Solriamfetol improves chronic sleep fragmentation-induced increases in sleep propensity and ameliorates explicit memory in male mice

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