Sexually dimorphic effects of postnatal allopregnanolone on the development of anxiety behavior after early deprivation.

Stress early in life exerts persistent detrimental effects on brain development. In this experiment, a rodent model of child neglect, early deprivation (ED), was used to investigate the role of the neurosteroid allopregnanolone [AlloP; 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP)] in the development of anxiety behavior. Subjects were either undisturbed controls or ED: separated individually for 6 h per day from postnatal day (PN) 2 to 6. Control and ED subjects were also either noninjected, vehicle-injected or injected with 5 mg/kg AlloP prior to the isolation. At PN 7, responses to 2.5 or 5 microg icv injections of AlloP were determined for separation-induced ultrasonic vocalizations (USVs). Tolerance to the USV-reducing effect of daily AlloP was seen in control but not ED pups, and daily AlloP reversed the expected ED suppression of USVs. As adults, controls treated with postnatal AlloP were less anxious than all other groups on the elevated plus maze. ED counteracted this effect. Male controls showed a reversal of the typical sex difference. There were no effects on open-field activity. These results suggest that the neonatal brain is responsive to alterations in AlloP levels, and that neuroactive progesterone metabolites may play a role in mediating the development of stress-related sex differences.