Estrogen receptor ligands counteract cognitive deficits caused by androgen deprivation in male rats

Androgen deprivation causes impairment of cognitive tasks in rodents and humans, and this deficit can be reverted by androgen replacement therapy. Part of the effects of androgens in the male may be mediated by their local metabolism to estradiol or 3-alpha androstanediol within the brain and the consequent activation of estrogen receptors. In this study we have assessed whether the administration of estradiol benzoate, the estrogen receptor beta selective agonist diaiylpropionitrile or the estrogen receptor alpha selective agonist propyl pyrazole triol affect performance of androgen-deprived male Wistar rats in the cross-maze test. In addition, we tested the effect of raloxifene and tamoxifen, two selective estrogen receptor modulators used in clinical practice. The behavior of the rats was assessed 2 weeks after orchidectomy or sham surgery. Orchidectomy impaired acquisition in the cross-maze test. Estradiol benzoate and the selective estrogen receptor beta agonist significantly improved acquisition in the cross-maze test compared to orchidectomized animals injected with vehicle. Raloxifene and tamoxifen at a dose of 1 mg/kg, but not at doses of 0.5 or 2 mg/kg, also improved acquisition of orchidectomized animals. Our findings suggest that estrogenic compounds with affinity for estrogen receptor beta and selective estrogen receptor modulators, such as raloxifene and tamoxifen, may represent good candidates to promote cognitive performance in androgen-deprived males. (C) 2011 Elsevier Inc. All rights reserved.