Related Experiment Video
Updated: Jun 16, 2026
Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice
Published on: July 12, 2024
[Delayed behavioral and morphological consequences in activation of the stress-antistress system in early ontogeny
Insights
Early life exposure to corticoliberin (CRH) and heat-shock protein 70 (HSP-70) in Wistar rats alters adult emotional and motor behaviors, with sex-dependent effects observed. These behavioral changes correlate with neuroanatomical alterations in brain regions like the substantia nigra.
Area of Science:
- Neuroscience
- Behavioral Endocrinology
- Pharmacology
Context:
- Early life stress and neurodevelopmental programming are critical.
- Corticoliberin (CRH) activates the stress system, while 70-kDa heat-shock protein (HSP-70) exhibits antistress properties.
- Investigating the long-term behavioral consequences of early-life neurochemical manipulation is essential.
Purpose:
- To investigate the long-term effects of early-life administration of CRH and HSP-70 on emotional and motor behaviors in adult Wistar rats.
- To determine if these effects are sex-dependent.
- To correlate behavioral changes with morphological alterations in limbic brain structures.
Summary:
- Wistar rat pups were administered CRH or HSP-70, and their adult behavior was assessed across multiple tests.
- Significant sex differences were observed, with males showing heightened sensitivity in certain anxiety and depression-related tests.
- CRH administration led to increased neuronal volume in the substantia nigra and ventral tegmental area, whereas HSP-70 caused neuronal degeneration and decreased density.
Impact:
- The study highlights sex-specific vulnerabilities to early-life stress and antistress interventions.
- Findings suggest that early-life CRH and HSP-70 exposure can induce lasting neurobiological changes affecting behavior.
- Results provide crucial insights for designing future research on pharmacological agents and their behavioral impact, considering sex and developmental timing.
Abstract:
Wistar rat pups aged 4-10-17 days were injected intraperitoneally with corticoliberin (corticotrophin-releasing hormone, CRH) in doses of 0.5 - 1.0 - 2.0 mg/rat, respectively (single administration for each rat), which activates the stress system, or with 70-kDa heat-shock protein (HSP-70) in doses of 5 - 10 - 20 mg/rat, respectively, which plays the role of intracellular shaperons and possesses antistress properties. The effect of drugs on the emotional and motor behavior was assessed in 5 tests (open field, elevated plus-maze, intruder-resident, Porsolt's depression test, and rotation test) in adult rats 90- 100-days-old. The activation of stress or antistress systems by CRH or HSP-70, respectively, changed the behavior of adult rats. These effects depended on the animal gender, being different in males and females: male rats were more sensitive in Porsolt's depression test, elevated plus-maze anxiety test, and rotation test, while being less sensitive in the open field and intruder-resident tests. These results indicate that the initial sensitivity of males and females with respect to CRH and HSP-70 is also different. The experimental data exhibited correlation with the results of morphological investigation of the limbic structures of the brain. In particular, CRH increased the relief (volume) of neurons of substantia nigra and ventral tegmental region without changing their density, while HSP-70 produced moderate degeneration of neurons and decreased their density. It is suggested the obtained data have to be taken into account in planning and conducting experimental investigations devoted to the influence of various pharmacological agents on the behavior.
