Bethany C. Reeb

Effects of Long-Term Estrogen Replacement on Social Investigation and Social Memory in Ovariectomized C57BL/6 Mice

Estrogen has been shown to play a role in modulating social recognition memory. However, the literature regarding the influence of estrogen on social memory is sparse and only covers two experimental manipulations: acute injections and receptor knockout. Long-term effects of estrogen replacement on social investigation and social recognition are unknown. Furthermore, existing social recognition protocols focus on memory of very short durations (<2 h). In the present study, we examined long-term effects of estrogen replacement on both short- (<30 min) and long-term (24 h) social recognition in ovariectomized female C57BL/6 mice by implanting 60-day time-release pellets containing physiological doses of estradiol (0, 0.18, or 0.72 mg of 17beta-estradiol). After 55 days of treatment, evidence of social recognition memory, measured by 24-h habituation, was found only in mice receiving the 0.72-mg pellet. This result is remarkable as previous reports indicate that individually-housed untreated rats and mice do not show habituation beyond 2 h. Our study further revealed that estrogen also increased frequencies of baseline social investigation without affecting general activity levels and decreased delayed post-swim-stress serum corticosterone concentration. Thus, these results suggest that long-term estrogen replacement increased the interest in social interaction as well as decreased stress responses. It is likely that the 24-h habituation observed in the estrogen replacement group is mediated jointly by the non-mnemonic effects of estrogen on the behavior displayed during the stage of memory encoding as well as mnemonic effects during the stage of memory consolidation.

Neonatal novelty exposure affects sex difference in open field disinhibition.

Neonatal stimulation induces sexually dimorphic changes at both the levels of behavior and neural systems. The effects of such stimulation on emotional reactivity measured by open field activity have been inconsistent. We found that among 23-day-old rats, neonatal novelty exposure induced an opposite pattern of sex difference in the initial open field disinhibition. This result suggests that the effect of early life stimulation on emotional reactivity is sex-dependent and that this early stimulation modulates the sexual dimorphism in emotional reactivity to a novel environment.

Sex difference in temporal patterns of social interaction and its dependence upon neonatal novelty exposure

Rodents have been an indispensable tool for the study of the neural mechanisms underlying a variety of emotional, social, and cognitive functions and dysfunctions. Surprisingly, little is known concerning sex difference in rodent social recognition memory and its sensitivity to neonatal stimulation. During the first 3 weeks of life, we exposed male and female neonates to a novel cage for 3-min per day while the matched littermate controls remained in the home cage. At 7 weeks and 7 months of age, we measured frequencies of social investigation over repeated social exposures and found that males showed greater habituation in social investigation than females during both juvenility and adulthood and that neonatal novelty exposure affected changes in the frequency of social investigation across multiple exposures in a sex-dependent manner. We speculate that these observed sex differences may reflect a sex difference in affinity for conspecific novelty rather than memory capability.

Developmentally stable sex-dependent modulation of turning asymmetry by neonatal novelty exposure

In rats, early life stimulation can enhance learning and memory and induce parallel changes in brain asymmetry. Despite persistent interest in human brain asymmetry, relatively little is known in animal models about developmental stability of early-experience effects on asymmetry and how early-experience may affect males and females differently in asymmetry measures across developmental stages. We exposed male and female neonatal rats to a novel cage for 3min per day during the first 3 weeks of life and measured spontaneous turning behavior at juvenility (7 weeks of age) and adulthood (7 months of age). We found that (1) the effects of such neonatal novelty exposure on turning bias are developmentally stable, and (2) neonatal novelty exposure differentially modulates turning bias in males and females. We briefly discuss implications of these findings in terms of the role of brain asymmetry in modulating cognitive and emotional development.