Mechanisms by which neonatal testosterone exposure mediates sex differences in impulsivity in prepubertal rats

Neonatal testosterone, either acting directly or through its conversion to estradiol, can exert organizational effects on the brain and behavior. The goal of the current study was to examine sex differences and determine the role of neonatal testosterone on prefrontal cortex-dependent impulsive choice behavior in prepubertal rats. Male and female prepubertal rats were tested on the delay-based impulsive choice task. Impulsive choice was defined as choosing an immediate small food reward over a delayed large reward. In a first experiment to examine sex differences, males made significantly more impulsive choices than did females. In a second experiment to examine the organizational effects of testosterone, females treated with neonatal testosterone made significantly more impulsive choices than did control females and their performance was indistinguishable from that of control males. In a third experiment to determine if the effect of testosterone on performance is due to the actions of androgens or estrogens through its conversion to estradiol, males treated neonatally with the aromatase inhibitor formestane, which blocks the conversion of testosterone to estradiol, females treated neonatally with the non-aromatizable androgen dihydrotestosterone, and females treated neonatally with estradiol made significantly more impulsive choices than did control females and their performance was indistinguishable from that of control males. Results indicate that male pubertal rats display increased impulsive choice behavior as compared to females, that this sex difference results from organizing actions of testosterone during the neonatal period, and that this effect can result from both androgenic and estrogenic actions.