Androgen Affects the Inhibitory Avoidance Memory by Primarily Acting on Androgen Receptor in the Brain in Adolescent Male Rats

Abstract

Adolescence is the critical postnatal stage for the action of androgen in multiple brain regions. Androgens can regulate the learning/memory functions in the brain. It is known that the inhibitory avoidance test can evaluate emotional memory and is believed to be dependent largely on the amygdala and hippocampus. However, the effects of androgen on inhibitory avoidance memory have never been reported in adolescent male rats. In the present study, the effects of androgen on inhibitory avoidance memory and on androgen receptor (AR)-immunoreactivity in the amygdala and hippocampus were studied using behavioral analysis, Western blotting and immunohistochemistry in sham-operated, orchiectomized, orchiectomized + testosterone or orchiectomized + dihydrotestosterone-administered male adolescent rats. Orchiectomized rats showed significantly reduced time spent in the illuminated box after 30 min (test 1) or 24 h (test 2) of electrical foot-shock (training) and reduced AR-immunoreactivity in amygdala/hippocampal cornu Ammonis (CA1) in comparison to those in sham-operated rats. Treatment of orchiectomized rats with either non-aromatizable dihydrotestosterone or aromatizable testosterone were successfully reinstated these effects. Application of flutamide (AR-antagonist) in intact adolescent rats exhibited identical changes to those in orchiectomized rats. These suggest that androgens enhance the inhibitory avoidance memory plausibly by binding with AR in the amygdala and hippocampus.

On the role of sex steroids in biological functions by classical and non-classical pathways. An update

“…Orchiectomized rats spent significantly less time in the illuminated box after foot-shock training and had reduced AR-immunoreactivity in amygdala/hippocampal CA1 region in comparison to sham-operated males. The treatment of these male rats with both T and DHT reversed these effects which suggest that androgens enhance inhibitory avoidance memory probably by binding to AR ( Islam et al, 2021 ).…”