Human studies suggest that childhood trauma predisposes individuals to develop stress-related disorders such as depression and post-traumatic stress disorder (PTSD). Recent years have witnessed growing interest in effectively modeling in animals the long-term effects of childhood emotional trauma on stress responses in adulthood. Most studies concerned with the impact of early-life stress on subsequent stress responses in adulthood in rodents have focused on the post-natal pre-weaning period. However, psychiatric studies often refer to human childhood rather than infancy when investigating the patients’ traumatic history of stress-related psychopathologies. In accordance with that, we have examined the consequences of stress exposure at a later early-life period, the post-weaning, pre-puberty (juvenile) period, which holds greater resemblance to human childhood. This review summarizes a series of studies examining the impact of exposure of rats to stressors during ‘juvenility’ (‘juvenile stress’) on the ability of these animals to cope with stress later in life. Exposure to relatively brief but significant stress experience during juvenility was found to impair the ability of animals to cope with stressful challenges in adulthood. These behavioral manifestations were associated with lasting alterations in limbic system brain regions of neuromodulatory pathways, such as alterations in the expression of cell adhesion molecules, GABAergic system functioning and alterations in levels of circulating corticosterone. Importantly, these studies have also demonstrated considerable individual and sex differences, which call for the development of adequate analysis approaches. The juvenile stress model combined with characterization of individual profiles is presented as a useful model to study in rodents different facets of stress-related disorders and neural mechanisms of vulnerability and resilience to stress.
Novel taste learning is a robust one-trial incidental learning process, dependent on functional activity of the insular (taste) cortex. In contrast to that of the cortex, the role of the hippocampus in taste learning is controversial. We set out to identify the time courses of the activation of mitogen-associated protein kinase (MAPK), transcription factor cAMP-response element-binding protein (CREB) and Akt/PKB (protein kinase B) in the insular cortex and hippocampus of rats subsequent to novel taste learning. Following taste learning, an early response (20 min) occurred at the same time in the insular cortex and the hippocampus. However, whereas MAPK was activated specifically in the insular cortex, CREB and Akt were phosphorylated in the hippocampus but not in the cortex. In addition, the immediate early gene, CCAAT/enhancer binding protein (C/EBPbeta) was induced in both the hippocampus and the insular cortex 18 h following taste learning. The results demonstrate, for the first time, correlative activation and gene expression in the hippocampus following novel taste learning. Moreover, the results suggest that different signal transduction cascades necessary for taste learning are activated in concert in different brain structures, to enable taste learning and consolidation.
Profound evidence indicates that GABAA receptors are important in the control of physiological response to stress and anxiety. The alpha subunit type composition contributes significantly to the functional characterization of the GABAA receptors. The alpha2, alpha3, alpha5 subunits are predominately expressed in the brain during embryonic and early postnatal periods of normal rats, whilst alpha1 are most prominent during later developmental stages. In the present study, we examined the long-term effects of juvenile stress on GABA alpha subunit expression in adulthood in the amygdala and hippocampus. We applied the elevated platform stress paradigm at juvenility and used the open-field and startle response tests to assess anxiety level in adulthood. Juvenile stress effects without behavioural tests in adulthood were also examined since previous studies indicated that the mere exposure to these tests might be stressful for rats, enhancing the effects of the juvenile exposure to stress. In adulthood, we quantitatively determined the level of expression of alpha1, alpha2 and alpha3 in the hippocampus and amygdala. Our results indicate that subjecting juvenile stressed rats to additional challenges in adulthood results in an immature-like expression profile of these subunits. To test for potential functional implications of these alterations we examined the effects of the anxiolytic (diazepam) and the sedative (brotizolam) benzodiazepines on juvenile stressed and control rats following additional challenges in adulthood. Juvenile stressed rats were more sensitive to diazepam and less sensitive to brotizolam, suggesting that the alterations in GABA alpha subunit expression in these animals have functional consequences.
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