Androgens Enhance Recognition Memory and Dendritic Spine Density in the Hippocampus and Prefrontal Cortex of Ovariectomized Female Rats

Abstract

Estrogen replacement has been repeatedly shown to enhance memory and increase dendritic spine density in the hippocampus and prefrontal cortex of ovariectomized (OVX) female rats. Given the potential deleterious effects of chronic estrogen administration, the present study assessed cognitive function using recognition memory tasks and measured dendritic spine density in the CA1 region of the hippocampus and medial prefrontal cortex after subchronic androgen replacement to adult OVX female rats. All androgens enhanced recognition memory in OVX rats, but object placement (OP) and object recognition (OR) results differed. Only testosterone enhanced OR. Testosterone had no effect on OP while dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and androstenedione (AD) enhanced OP. Dendritic spine density was increased by both TP and DHEA in both brain areas (DHT and AD were not tested). Lastly, we used the aromatase inhibitor, letrozole, to discriminate between potential androgenic and estrogenic effects of androgens on behavior. Letrozole alone did not alter recognition memory in OVX rats and did not block the effects of either TP or DHEA on recognition memory suggesting that effects were mediated via androgenic mechanisms. The present results expand previous information on gonadal hormone actions and show that, in addition to estrogens, androgens also improve memory and increase spine density in brains of OVX female rats. While requiring further investigation, these observations provide a basis for therapeutic interventions in the treatment of menopausal, age or disease related memory loss.

Keywords: androgens; dendritic spines; hippocampus; memory; neural plasticity; prefrontal cortex; testosterone.