Estrogen receptor α functions in the regulation of motivation and spatial cognition in young male rats.

Estrogenic functions in regulating behavioral states such as motivation, mood, anxiety, and cognition are relatively well documented in female humans and animals. In males, however, although the entire enzymatic machinery for producing estradiol and the corresponding receptors are present, estrogenic functions have been largely neglected. Therefore, and as a follow-up study to previous research, we sub-chronically applied a specific estrogen receptor α (ERα) antagonist in young male rats before and during a spatial learning task (holeboard). The male rats showed a dose-dependent increase in motivational, but not cognitive, behavior. The expression of hippocampal steroid receptor genes, such as glucocorticoid (GR), mineralocorticoid (MR), androgen (AR), and the estrogen receptor ERα but not ERβ was dose-dependently reduced. The expression of the aromatase but not the brain-derived neurotrophic factor (BDNF) encoding gene was also suppressed. Reduced gene expression and increased behavioral performance converged at an antagonist concentration of 7.4 µmol. The hippocampal and blood serum hormone levels (corticosterone, testosterone, and 17β-estradiol) did not differ between the experimental groups and controls. We conclude that steroid receptors (and BDNF) act in a concerted, network-like manner to affect behavior and mutual gene expression. Therefore, the isolated view on single receptor types is probably insufficient to explain steroid effects on behavior. The steroid network may keep motivation in homeostasis by supporting and constraining the behavioral expression of motivation.