Neonatal caffeine alters passive avoidance retention in rats in an age- and gender-related manner.

Chronic administration of an adenosine receptor antagonist disturbs spatial learning and memory in adult mice and neonatal caffeine exposure results in long-term behavioral and biochemical sequelae in mice and rats. We thus postulated that early treatment with caffeine would have latent effects on learning and memory as measured in a passive avoidance paradigm. Rats were not handled or received caffeine (15-20 mg/kg/day) by gavage over postnatal days 2-6. At 28 or 70-90 days of age, rats were trained to avoid an electrified grid and tested for retention 24 h, 72 h, and 7 days later. At 28 days, caffeine-exposed rats required more trials to meet criterion than did control rats, regardless of gender. There was minimal effect on retention of either neonatal treatment or gender at this age. At 70-90 days, there was no effect of either gender or treatment on learning; however, there was a significant effect of gender (P < 0.05) on retention at 24 h that was more pronounced in neonatally caffeine-treated rats (P < 0.01). At 72 h, the effect of caffeine on retention differed between male and female rats. Neonatal caffeine exposure significantly improved retention in females (P < 0.01) and significantly decreased retention in males (P < 0.05). Thus, caffeine exposure limited to the first week of life resulted in alterations in passive avoidance retention that became apparent over pubertal development. These changes were a function of the gender of the animal.