Short- and long-term neurobehavioural impairments in mice offspring following chronic perinatal caffeine exposure and withdrawal

This study explored neurodevelopmental and adult neurobehavioural outcomes in mouse offspring following chronic perinatal caffeine exposure and subsequent withdrawal. Healthy adult female BALB/c mice were mated and, at gestational day (GD) 10, were randomly assigned to one of three groups (n = 4): control, low-dose caffeine, and high-dose caffeine. The caffeine-exposed groups received either a low (50 mg/kg) or high (100 mg/kg) dose of caffeine daily via oral gavage from GD 10 until the end of lactation at postnatal day (PND) 21, whereas the control group received sterile water. At PND 21, a subset of offspring from the caffeine-exposed and control groups underwent neurodevelopmental behavioural assessments, including negative geotaxis, cliff avoidance, and surface righting tests, to evaluate the effects of chronic perinatal caffeine exposure on sensorimotor reflex functions. The remaining offspring were allowed to grow into adulthood and, at three months of age, underwent neurobehavioural assessments to evaluate motor function, anxiety-like behaviour, and cognition via the pole test, open field test, and Morris water maze (MWM) test. Compared with those in the high-dose caffeine group, the mice in the low-dose caffeine group had accelerated attainment of neurological milestones, such as the righting reflex and cliff avoidance. Conversely, compared with the control and low-dose caffeine treated offspring, the high-dose caffeine-treated offspring presented delayed eye opening and impaired negative geotaxis. However, there were no significant differences between the caffeine-exposed and control groups in the adult neurobehavioural assessments following caffeine withdrawal. These findings suggest that perinatal caffeine exposure can influence early neurodevelopmental processes but does not seem to have persistent effects on motor function, cognition, or anxiety in adulthood. This study underscores the transient nature of caffeine’s impact on brain development and highlights the need for further research to explore the long-term consequences of prenatal caffeine exposure.