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The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Chronic corticosterone treatment impairs trace conditioning in rats with a neonatal medial prefrontal cortex lesion
1Brain Research Institute, Department of Neuropharmacology, University of Bremen, FB2 P.O. Box 330440, 28334 Bremen, Germany. thenkel@uni-bremen.de
Abstract:
In contrast to adult lesions, which usually result in immediate functional deficits, neonatal lesions of the medial prefrontal cortex (PFC) in rats can be compensated to some extent by functional tissue during ontogeny with sparing of function in many aspects. In this study, we examined the effects of a neonatal ibotenic acid lesion of the medial PFC on trace conditioning in adult rats, a form of classical conditioning. Since the PFC is also part of the neuroendocrine stress regulation, we additionally investigated the effects of chronic pubertal corticosterone treatment on trace conditioning to test the hypothesis that early lesions render the brain vulnerable to stress-like conditions in later life. Although there was considerable regeneration of much of the lesioned tissue in the medial PFC, a disruption of cortical layering and cortical thinning was observed in the adult brain. The chronic corticosterone treatment led to a decrease of corticosterone blood serum levels and reduced adrenal weights. Neither the neonatal lesion nor the corticosterone treatment alone affected trace conditioning; however, in rats that had received both treatments trace conditioning was impaired, suggesting synergistic effects between the lesion and the glucocorticoid treatment. An interaction between two adverse events that occur at different life stages complies with neurodevelopmental theories for some psychiatric diseases like schizophrenia.
Insights
Neonatal medial prefrontal cortex (PFC) lesions combined with pubertal corticosterone treatment impaired trace conditioning in adult rats. This suggests early brain injury may increase vulnerability to later life stress.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Behavioral Neuroscience
Background:
- Neonatal medial prefrontal cortex (PFC) lesions can be compensated during development, unlike adult lesions.
- The PFC plays a role in neuroendocrine stress regulation.
- Early life adversity is linked to later psychiatric disorders.
Purpose of the Study:
- To investigate the long-term effects of neonatal medial PFC lesions on trace conditioning.
- To examine if chronic pubertal corticosterone treatment exacerbates deficits caused by early lesions.
- To test the hypothesis that early lesions increase vulnerability to stress.
Main Methods:
- Neonatal ibotenic acid lesions of the medial PFC in rats.
- Trace conditioning paradigms in adult rats.
- Chronic pubertal corticosterone administration.
- Assessment of brain morphology (cortical layering, thinning) and corticosterone levels.
Main Results:
- Despite tissue regeneration, neonatal lesions caused structural changes in the medial PFC.
- Corticosterone treatment reduced serum corticosterone levels and adrenal weights.
- Neither lesion nor corticosterone alone impaired trace conditioning.
- Combined lesion and corticosterone treatment significantly impaired trace conditioning.
Conclusions:
- Neonatal medial PFC lesions and pubertal corticosterone treatment have synergistic adverse effects on trace conditioning.
- Early life brain insults may predispose individuals to stress-related functional deficits later in life.
- Findings align with neurodevelopmental theories of psychiatric disorders.
