Juvenile male rats display lower cortical metabolic capacity than females.

The juvenile brain undergoes marked maturational changes accompanied by major sex hormone changes. In particular, sex differences in neural substrates could underlie male-specific dysfunction in behavioral responses related to the prefrontal cortex. Sex differences in regional metabolic capacity of the cerebral cortex were investigated in juvenile Sprague-Dawley rats. At 6 weeks of age the brains were processed for quantitative histochemistry of cytochrome oxidase, a rate-limiting enzyme in cellular respiration, which is an index of brain metabolic capacity. Quantitative image analysis revealed a main effect of sex with males displaying lower regional metabolic capacity than females in the dorsolateral and orbital prefrontal cortex and in the posterior parietal cortex. In addition, males separated for 6 h/day from their mothers as pups showed greater ambulatory behavior in the novel open field and higher metabolism in the posterior parietal cortex relative to males separated for 15 min/day. This is the first study to show sex differences in brain metabolic capacity in regions such as the prefrontal cortex that may be hypometabolic in juvenile males relative to females.