neonatal caffeine exposure and seizure susceptibility in adult rats early developmental exposure to caffeine in rats results in changes in brain excitability that persist to adulthood the mechanism of these alterations is unknown to identify potential neurotransmitter systems involved we exposed neonatal rats to caffeine and determined seizure thresholds for chemoconvulsants active at different cns receptors in the adult animal rats were unhandled nh or received by gavage 005 ml10 g either vehicle water or caffeine 1520 mgkgday for postnatal days 26 at age 7090 days each rat was infused intravenously iv with picrotoxin pic bicuculline bic convulsants acting at the gammaaminobutyric acidbenzodiazepine gababdz receptor pentylenetetrazol ptz possibly acting at both gababdz and nmethyldaspartate nmda receptors caffeine acting at adenosine receptors strychnine str acting at glycine receptors or kainic acid ka acting at the nmda receptor seizure thresholds were analyzed as a function of neonatal treatment and sex thresholds for caffeine ptz pic and ka were increased as a function of neonatal caffeine exposure p 001 002 002 and 0005 respectively the thresholds for bic and str were not altered there were also gender differences in seizure susceptibility thresholds for seizures produced by bic caffeine pic and str were higher in females p 0005 0005 0001 and 00001 respectively but were not different for seizures caused by ptz these results suggest that early developmental exposure to caffeine affects later seizure susceptibility moreover some of these effects are gender specific