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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats
Meng-Chang Ko1, Yu-Hui Hung1, Pei-Yin Ho2
1Department of Life Science,National Taiwan Normal University,Taipei,Taiwan.
Insights
Neonatal dexamethasone (DEX) exposure in rats leads to adult depression-like behaviors and altered amygdala function. MAPK signaling in the lateral amygdala is implicated in these adverse effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Synthetic glucocorticoids like dexamethasone (DEX) treat chronic lung disease in premature infants.
- Neonatal DEX exposure may adversely affect brain development and cognitive function.
- The amygdala's role in emotion and plasticity suggests potential long-term impacts of neonatal DEX.
Purpose of the Study:
- To investigate the long-term effects of neonatal DEX treatment on amygdala synaptic function in adult rats.
- To explore the involvement of MAPK signaling in DEX-induced changes in amygdala function.
Main Methods:
- Neonatal Wistar rats received tapering doses of DEX from postnatal days 1-3.
- Adult rats (8 weeks old) underwent forced swimming tests (FST) and electrophysiological recordings.
- MAPK inhibitor PD98059 was administered intracerebroventricularly to assess its rescue effects.
Main Results:
- Neonatal DEX treatment increased depression-like behavior in adult rats, evidenced by increased free-floating time in FST.
- DEX exposure elevated long-term potentiation (LTP) and MAPK phosphorylation in the lateral amygdala (LA).
- Inhibition of MAPK signaling with PD98059 rescued depression-like behavior and normalized LTP.
Conclusions:
- MAPK signaling cascade in the lateral amygdala (LA) mediates the adverse effects of neonatal DEX treatment.
- Neonatal DEX exposure can lead to long-term amygdala dysfunction, increasing susceptibility to depressive disorders in adulthood.
Abstract:
Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life.
