ABERRANT MATERNAL-BEHAVIOR IN MICE TREATED WITH A PROGESTERONE-RECEPTOR ANTAGONIST DURING PREGNANCY

The rapid onset of normal maternal behaviour after parturition in mice , consisting of cleaning, warming, feeding and protection of offspring , is primed by oestrogen, progesterone and oxytocin. Previous studies showed that passive transfer of monoclonal antibodies against progeste rone significantly increases the incidence of maternal rejection of pu ps. To test the hypothesis that aberrant maternal behaviour is due to partial progesterone withdrawal leading to hormonal imbalance during l ate pregnancy, maternal rejection was assessed following treatment wit h a progesterone receptor antagonist. Mifepristone (RU486) was given s ubcutaneously on either day 2 (100 mu g) or day 17 (50 mu g) of pregna ncy, or on the first day of lactation (100 mu g). Maternal behaviour w as monitored twice daily for the first 6 days of lactation and pup rej ection recorded for a further 15 days. Maternal rejection was signific antly greater after mifepristone administration on either day 2 or day 17 (28.6% and 38.3%) compared with controls (11.1% and 5.2% respectiv ely). Rejection was negligible in both treated and control groups if m ifepristone was given after parturition. When mothers were treated at day 17, the length of the latent period before pups were retrieved and returned to the nest was markedly increased in mifepristone-treated m others (46.3 s) compared with controls 4.4 s) though the effect was tr ansient. The results indicate that mifepristone interferes with the ho rmonal priming mechanism(s) necessary for the onset of normal maternal behaviour by a receptor-mediated effect. The similarity of the presen t results and those obtained with anti-progesterone antibodies implies that receptor antagonism or antibody scavenging of progesterone influ ence a common central nervous mechanism that is essential for the norm al priming process.