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

Abstract

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.

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.…”

The Influence of Cross-Fostering on Alcohol Consumption and Depressive-Like Behaviors in HA and LA Mice: The Role of the Endogenous Opioid System

“…Moreover, a 6% ethanol solution does not produce aversive effects, which also justifies our assumption. As reported in different studies [ 58 , 59 ], another limitation of the presented experiment may be relatively low control of litter effect, since as mentioned above we used offspring from only two different litters. However, based on our previous reports, we know that ethanol intake and preference are similar across litters within HA and LA lines [ 11 , 12 , 20 ].…”

Early life esophageal acid exposure reduces expression of NMDAR1 in the adult rat dorsal hippocampus and medial prefrontal cortex: Potential relationship with hyperlocomotion

“…Male Sprague-Dawley rats were administered with an esophageal acid or saline infusion once per day (postnatal days [7][8][9][10][11][12][13][14]. Some of these rats were given acute esophageal acid rechallenge in adulthood (postnatal day 60).…”

“…The spontaneous locomotor behavior test has been used in numerous studies on psychosis to assess general activity in rats and to reflect the activity of the central nervous system. 12,13 It is important to discern whether changed spontaneous locomotor behavior (including locomotion, locomotor activity and locomotor sensitivity) is the result of complex neuroadaptation (neuroplasticity) in the central nervous system. [14][15][16] To the best of our knowledge, there are no published reports on spontaneous locomotor activity in rats after noxious esophageal stimulation in early life.…”