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      Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning

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          Abstract

          We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern.

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          Most cited references36

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          Chronic stress alters dendritic morphology in rat medial prefrontal cortex.

          Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. Medial prefrontal cortex is a target for glucocorticoids involved in the stress response. We have previously demonstrated that 3 weeks of daily corticosterone injections result in dendritic reorganization in pyramidal neurons in layer II-III of medial prefrontal cortex. To determine if similar morphological changes occur in response to chronic stress, we assessed the effects of daily restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were exposed to either 3 h of restraint stress daily for 3 weeks or left unhandled except for weighing during this period. On the last day of restraint, animals were overdosed and brains were stained using a Golgi-Cox procedure. Pyramidal neurons in lamina II-III of medial prefrontal cortex were drawn in three dimensions, and the morphology of apical and basilar arbors was quantified. Sholl analyses demonstrated a significant alteration of apical dendrites in stressed animals: overall, the number and length of apical dendritic branches was reduced by 18 and 32%, respectively. The reduction in apical dendritic arbor was restricted to distal and higher-order branches, and may reflect atrophy of terminal branches: terminal branch number and length were reduced by 19 and 35%. On the other hand, basilar dendrites were not affected. This pattern of dendritic reorganization is similar to that seen after daily corticosterone injections. This reorganization likely reflects functional changes in prefrontal cortex and may contribute to stress-induced changes in cognition. Copyright 2004 Wiley Periodicals, Inc.
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            Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus.

            Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress.
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              Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment.

              Chronic restraint stress causes significant dendritic atrophy of CA3 pyramidal neurons that reverts to baseline within a week. Therefore, the authors assessed the functional consequences of this atrophy quickly (within hours) using the Y maze. Experiments 1-3 demonstrated that rats relied on extrinsic, spatial cues located outside of the Y maze to determine arm location and that rats with hippocampal damage (through kainic acid, colchicine, or trimethyltin) had spatial memory impairments. After the Y maze was validated as a hippocampally relevant spatial task, Experiment 4 showed that chronic restraint stress impaired spatial memory performance on the Y maze when rats were tested the day after the last stress session and that tianeptine prevented the stress-induced spatial memory impairment. These data are consistent with the previously demonstrated ability of tianeptine to prevent chronic stress-induced atrophy of the CA3 dendrites.
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                Author and article information

                Journal
                Neurosci J
                Neurosci J
                NEUROSCIENCE
                Neuroscience journal
                Hindawi Publishing Corporation
                2314-4262
                2314-4270
                2015
                16 April 2015
                : 2015
                : 697659
                Affiliations
                1Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
                2Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA
                Author notes

                Academic Editor: Jose Cimadevilla

                Article
                10.1155/2015/697659
                4437338
                52a3e4bc-fc3e-4cdb-b451-282d0541f932
                Copyright © 2015 Angela L. McDowell et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 January 2015
                : 23 March 2015
                : 25 March 2015
                Categories
                Research Article

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