Here we have investigated the effects of maternal caffeine intake (1 g/l) on MK-801-induced hyperlocomotion in rat pups. Animals submitted to caffeine treatment during the gestational and lactational period were separated in two groups: caffeine-treated group (up to 21 days old) and washout group (caffeine treatment up to 7 days old). MK-801 (0.25 mg/kg, i.p.) promoted hyperlocomotion in control rats, but this stimulatory effect was significantly decreased in caffeine-treated and washout groups. The permanent effect after caffeine withdrawal suggests durable or adaptive changes during neurodevelopment, mainly on adenosine receptors or neurotransmitter systems modulated by adenosine, such as the glutamatergic system.