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

Abstract

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.

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

“…The assessment of leucocyte phagocytic activity revealed a trend to impairment of this capacity after the METH treatment in the adult age. Impaired leucocyte phagocytosis after prenatal modafinil administration was already observed in our earlier study (Ruda‐Kucerova et al, 2017). Therefore, our data seem to contradict.…”

“…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).…”

Diffusion kurtosis imaging detects the time‐dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease

“…In a brightly lit room, mice were individually tested for locomotor in OF using the Actitrack system (Panlab) as previously described (Ruda‐Kucerova et al., 2017; Ruda‐Kucerova, Amchova, et al., 2018; Ruda‐Kucerova, Pistovcakova, et al., 2018). Each Plexiglas arena (45 × 45 × 30 cm) was surrounded by two frames equipped with photocells located one above another at 2 and 7 cm over the cage floor.…”

Sleep Pharmacotherapy for Common Sleep Disorders in Pregnancy and Lactation

“…Table 3 summarizes the data available on stimulants and rapid eye movement suppressants. 24,[82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] Mothers should be counseled about the potential teratogenic risk of some drugs and the association of drug use with other adverse outcomes such as behavioral changes or longterm neurodevelopment impairment. 24 Based on recent registry data, modafinil is associated with major congenital anomalies.…”

“…Limited reports of no adverse effects on the nursling Modafinil See details regarding armodafinil and major congenital malformations. Limited animal data suggest alteration in immune and behavioral effects that enhance vulnerability to development of behavioral sensitization in adulthood in prenatally exposed mice 90,91 Human data available on transfer to breast milk are limited. 92 The drug's small molecular weight makes it likely to be transferred into breast milk.…”