RESUMO
It is well known that neonatal pro-inflammatory challenge (NPC) acquire a predisposition to the development of a number of neuropsychiatric diseases: depression, anxiety disorders, autism, attention deficit hyperactivity disorder. Symptoms of these diseases can manifest themselves in adulthood and adolescent after repeated exposure to negative influences. Preventing the development of the negative consequences of NPC is one of the main tasks for researchers. The exposure to an enriched environment (EE) was shown to have anxiolytic, anti-depressive, and pro-cognitive effects. The present work was aimed to investigate the effects of the long-term EE on anxious-depressive and conditioned fear behavior in normal male and female rats and subjected to NPC. The NPC was induced by subcutaneous administration of lipopolysaccharide (LPS, 50 µg/kg) on 3d and 5th PNDs. The control animals received saline (SAL). The rats were placed in the EE from 25 to 120 PND. Animals housed in the standard conditions (STAND) served as controls. In adult female and male rats of the STAND groups, LPS did not affect the anxiety, depressive-like behavior and conditioned fear. The EE increased motor and search activity in males and females. In the open field, the EE reduced anxiety in males of the SAL and LPS groups and in females of SAL groups compared to the STAND housed animals. In the elevated plus maze, the EE decreased anxiety only in males of the SAL group. In the sucrose preference test, the EE did not change sucrose consumption in males and females of SAL and LPS groups, while, in the forced swimming test, the EE reduced depressive-like behavior in females of both SAL and LPS groups. The enrichment decreased the contextual conditioned fear in male and female of SAL groups, but not of the LPS group, and did not affect the cue conditioned fear. The corticosterone reactivity to the forced swimming stress increased in males of the EE groups. The basal level of IL-1beta in blood serum decreased in males of the SAL-EE group. Thus, the EE reduced anxiety in males, depressive-like behavior in females, and contextual conditioned fear in males and females compared to the STAND housed animals. Although the NPC did not affect these behaviors in the STAND groups, LPS prevented the beneficial EE effects on anxiety and conditioned fear. The opposing effects of LPS were dependent on sex and type of testing.
RESUMO
Goal of the current work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide-induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures. Relevance of this study is related to poor understanding of the effects of acute and chronic stress on manifestation of cognitive brain functions, as well as ambiguity of the literature data on the effects of both stresses on hypothalamic pituitary axis and expression of the proinflammatory cytokine genes. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze. For the period of learning, the rats under acute stress swam on average less distance to reach a hidden platform, spent less time in the peripheral zone of the pool (thigmotaxis), and had low speed compared to the control animals and to the group of rats under chronic LPS-induced stress. In the test without a platform in the pool there were no significant differences between the groups on the time spent in the platform quadrant and distance swum. Acute stress caused substantial increase of the TNF-α and IL-1ß mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Although chronic stress increased the levels of the TNF-α and IL-1ß mRNA in the amygdala and hippocampus compared to the control groups, significance between the groups was only marginal and BDNF concentration did not differ from the control animals in any of the brain structures mentioned. Expression of the IL-6 mRNA only marginally increased in the amygdala of the animals under the acute LPS-induced stress and marginally decreased in the animals under chronic LPS stress in the hippocampus relative to the control groups. In total, the most pronounced molecular-biochemical changes occurred in the amygdala and hippocampus, where increase of the expression of the TNF-α and IL-1ß interleukins mRNAs were observed in the animals under acute and chronic LPS-induced stress and no changes in the BDNF mRNA concentration were observed in the frontal lobe.
