LAUSR

&NA; Few studies have addressed the effects of caffeine in the puberty and/or adolescence in a sex dependent manner. Considering that caffeine intake has increased in this population, we investigated the behavioral and synaptic proteins changes in pubescent male and female rats after maternal consumption of caffeine. Adult female Wistar rats started to receive water or caffeine (0.1 and 0.3 g/L in drinking water; low and moderate dose, respectively) during the active cycle at weekdays, two weeks before mating. The treatment lasted up to weaning and the offspring received caffeine until the onset of puberty (30–34 days old). Behavioral tasks were performed to evaluate locomotor activity (open field task), anxious‐like behavior (elevated plus maze task) and recognition memory (object recognition task) and synaptic proteins levels (proBDNF, BDNF, GFAP and SNAP‐25) were verified in the hippocampus and cerebral cortex. While hyperlocomotion was observed in both sexes after caffeine treatment, anxiety‐related behavior was attenuated by caffeine (0.3 g/L) only in females. While moderate caffeine worsened recognition memory in females, an improvement in the long‐term memory was observed in male rats for both doses. Coincident with memory improvement in males, caffeine increased pro‐ and BDNF in the hippocampus and cortex. Females presented increased proBDNF levels in both brain regions, with no effects of caffeine. While GFAP was not altered, moderate caffeine intake increased SNAP‐25 in the cortex of female rats. Our findings revealed that caffeine promoted cognitive benefits in males associated with increased BDNF levels, while females showed less anxiety. Our findings revealed that caffeine promotes distinct behavioral outcomes and alterations in synaptic proteins during brain development in a sex dependent manner. HighlightsFemale pubescent rats were more responsive to caffeine‐induced hyperlocomotion.Caffeine worsened recognition memory in female pubescent rats.Recognition memory was improved by caffeine in male pubescent rats.Anxiety‐related behavior was attenuated by caffeine in female pubescent rats.Both pro‐ and BDNF increased in the hippocampus after caffeine treatment in males.