The influence of social subordinate housing on the withdrawal effects from progesterone and estradiol in male rats

Abstract

Chronic stress and its concomitant neurobiological consequences are, in all probability, provocateurs of mental disease in humans. To gain some insight into the provocative effects of stress on hormonally dependent conditions, we developed a rat model that combines social subordinate housing (SSH) with withdrawal from combined progesterone (P) and estradiol (E) treatment (PEWD). At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (35 days old) and two older rats (55 days old), with the intent of producing subordination stress in the younger animals. Triads containing three 35-day-old rats were used as age controls. Subordination stress was assessed with the elevated plus maze (EPM) and by corticosterone (CORT) analysis. Social rank within the triads was determined using a food competition test (FCT) and a tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5mg/kg P combined with 10 μg/kg E, or placebo (vehicle). Twenty-four hours after the last injection, the subordinate and dominant animals were tested in an open-field test (OFT) and a social challenge test (SCT). The SCT consisted of a 10-min exposure to three unfamiliar rats. SSH increased baseline CORT levels and reduced EPM open-arm time and post-EPM CORT levels compared to age-control rats. Only in the subordinate animals did PEWD increase locomotor activity and digging behavior, and reduce wrestling and pinning behavior. The behavioral results indicate an interaction between the effects of the lasting social subordinate stress and PEWD.