Anti-progesterone effects on maternal recognition and behaviour imprinted during first pregnancy in mice

Anti-progesterone treatment using specific anti-progesterone antibodies or a progesterone receptor (PR) antagonist during first pregnancy impairs postpartum maternal behaviour in mice. This effect is demonstrable only if the treatment is given during pregnancy but not immediately after parturition. The purpose of the present studies was to investigate if maternal behaviour is also impaired by anti-progesterone treatment in subsequent pregnancies. Studies with a monoclonal antibody to progesterone (DB3; 4.5 nmol/mouse) showed that injection of females on day 17 of second pregnancy did not cause maternal rejection but the latency of pup retrieval was prolonged especially during the first 3 days of lactation. This phenomenon was not observed in animals that had previous experience of full length lactation. Experiments were carried out with mifepristone (RU486; 10 micrograms/mouse) injected at day 17 of first, second or third pregnancies. Pup rejection (22.5% vs 12.3%) and prolongation of the retrieval latency (62.3 +/- 13.3 vs 19.7 +/- 6.5 s; P < 0.02) were observed following the first pregnancy. No abnormal behavioural effects were found in mothers treated in second or third pregnancy who had prior full length lactation experience. Control females subjected to only one pup retrieval test after first delivery rejected their pups if treated in their second pregnancy (27.3% vs 4.4%; P < 0.001) and displayed a marginal prolongation of the retrieval latency period (20.9 +/- 7.0 vs 7.4 +/- 2.6 s). Anti-progesterone treatment had no negative influence when administered during third pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)