Related Experiment Video
Updated: Jul 30, 2026
Handling Techniques to Reduce Stress in Mice
Published on: September 25, 2021
Gender specific effect of neonatal handling on stress reactivity of adolescent rats
M K Park1, T A Hoang, J D Belluzzi
1Department of Pharmacology, College of Medicine and Transdisciplinary Tobacco Use Research Center, University of California, Irvine, CA 92697, USA. minjungp@uci.edu
Insights
Neonatal handling dampens stress responses in male rats but enhances them in females. This gender-specific effect on stress reactivity and brain activity highlights the importance of sex as a biological variable in early life stress research.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Psychology
Background:
- Early life experiences, such as neonatal handling, can have long-lasting effects on stress responses.
- Most research has focused on adult male offspring, leaving the effects on females and adolescents understudied.
- Adolescence is a critical period for the development of stress responsivity.
Purpose of the Study:
- To investigate the impact of neonatal handling on the endocrine stress response and brain activity in adolescent male and female rats.
- To determine if the effects of neonatal handling on stress reactivity differ between sexes during adolescence.
Main Methods:
- Rat pups were subjected to handling or no handling during the early neonatal period.
- Adolescent male and female rats were exposed to acute restraint stress.
- Plasma hormone levels (e.g., corticosterone) and brain activity (c-fos mRNA expression in the posterior cingulate cortex) were measured.
Main Results:
- Neonatal handling reduced stress-induced hormone levels in adolescent males, consistent with previous findings in adults.
- In contrast, handled adolescent females exhibited elevated plasma hormone concentrations in response to stress.
- Handled females showed increased stress-induced activation of the posterior cingulate cortex compared to controls.
Conclusions:
- Neonatal handling exerts a gender-specific influence on the endocrine and neural stress responses during adolescence.
- The findings underscore the importance of considering sex as a critical variable when examining the long-term consequences of early life manipulations on stress responsivity.
Abstract:
Early neonatal handling of rat pups produces dampened hypothalamic-pituitary-adrenal axis reactivity to stress in adult male offspring. However, less is known about whether there is a similar effect for females. Although, most studies of neonatal handling have examined subsequent effects during adulthood, adolescence is an important developmental stage for stress responsivity. To address these issues, the effect of neonatal handling on the endocrine stress response and brain activity of male and female rats was determined in response to acute restraint stress during adolescence. Consistent with previous findings in adult males, neonatal handling reduced restraint stress-induced hormone levels in adolescent males. However, in contrast, we found elevated plasma hormone concentrations in handled females. A gender-specific handling effect on brain activity was also evident, with significantly increased stress-induced activation of the posterior cingulate cortex of handled females, as measured by c-fos mRNA expression. The striking gender difference in the effect of early neonatal handling provides evidence that this must be considered as an important variable in subsequent stress responsivity induced by early manipulations.
