Chronic corticosterone treatment impairs trace conditioning in rats with a neonatal medial prefrontal cortex lesion.
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.
Brain Research Institute, Department of Neuropharmacology, University of Bremen, FB2 P.O. Box 330440, 28334 Bremen, Germany. thenkel@uni-bremen.de
Thomas
T
Enkel
Michael
M
Koch
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003214:Conditioning, Classical; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
D007051:Ibotenic Acid; D003345:Corticosterone