Inhibition of aggression by progesterone and its metabolites in female Syrian hamsters

The sequence of estradiol and progesterone is known to inhibit the expression of aggression in female hamsters. Despite the key importance of progesterone in the inhibition of aggression, little is known of the mechanisms through which progesterone may exert this effect. Three experiments were performed to assess the degree to which metabolites of progesterone can affect aggression in female Syrian hamsters. Systemic estradiol treatment followed by injections of either progesterone (300 μg IP) or 4‐pregnen‐21‐ol‐3,20‐dione (DOC, 300 μg IP) reliably inhibited aggression. Systemic injection (75, 150, or 300 μg IP) of either 5α‐pregnan‐3α,21‐diol‐20‐one (THDOC) or 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP) did not affect aggression. Intracerebroventricular infusion of 3α,5α‐THP following systemic estradiol treatment also did not affect aggression. In a third experiment, female hamsters were given systemic treatments with estradiol and progesterone that were subthreshold with respect to inhibition of aggression. In these females, intracerebroventricular infusion of THDOC inhibited aggression. These results indicate that metabolites of progesterone can inhibit aggression, most notably in synergy with progesterone itself. Aggr. Behav. 27:372–381, 2001. © 2001 Wiley‐Liss, Inc.