Impaired imprinting and social behaviors in chicks exposed to mifepristone, a glucocorticoid receptor antagonist, during the final week of embryogenesis

The effects of glucocorticoid receptor dysfunction during embryogenesis on the imprinting abilities and social behaviors of hatchlings were examined using "fertile hen's egg-embryo-chick" system. Methods and results: Of embryos treated with mifepristone (0.4. μmol/egg) on day 14, over 75% hatched a day later than the controls (day 22) without external anomalies. The mifepristone-treated hatchlings were assayed for imprinting ability on post-hatching day 2 and for social behaviors on day 3. The findings were as follows: imprinting ability (expressed as preference score) was significantly lower in mifepristone-treated hatchlings than in controls (0.65. ± 0.06 vs. 0.92. ± 0.02, P< 0.005). Aggregation tests to evaluate the speed (seconds) required for four chicks, individually isolated with cardboard dividers in a box, to form a group after removal of the barriers showed that aggregation was significantly slower in mifepristone-treated hatchlings than in controls (8.7. ± 1.1 vs. 2.6. ± 0.3, P< 0.001). In belongingness tests to evaluate the speed (seconds) for a chick isolated at a corner to join a group of three chicks placed at the opposite corner, mifepristone-treated hatchlings took significantly longer than controls (4.5. ± 0.4/40. cm vs. 2.4. ± 0.08/40. cm, P< 0.001). In vocalization tests, using a decibel meter to measure average decibel level/30. s (chick vocalization), mifepristone-treated hatchlings had significantly weaker vocalizations than controls (14.2. ± 1.9/30. s vs. 26.4. ± 1.3/30. s P< 0.001). In conclusion, glucocorticoid receptor dysfunction during the last week embryogenesis altered the programming of brain development, resulting in impaired behavioral activities in late life.