Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

Abstract

Chronic stress facilitates fear conditioning in rats with hippocampal neuronal atrophy and in rats in which the atrophy is prevented with tianeptine, a serotonin re-uptake enhancer. The purpose of this study was to determine whether the lack of dissociation between fear conditioning performance and hippocampal integrity was masked by the presence of endogenous corticosteroids during training. As in previous studies, rats were stressed by daily restraint (6 h/day for 21 days), trained in the conditioning chamber (day 23), and then assessed for conditioned fear (day 25) at a time when hippocampal dendritic atrophy persists. On the training day, half of the control and stressed rats were injected with metyrapone to reduce corticosterone release. Two hours later, two paired or unpaired presentations of tone and footshock were delivered. Although metyrapone reduced conditioned fear in all rats, only stressed rats showed dissociated fear conditioning (i.e. tone conditioning was reduced while contextual conditioning was eliminated). Chronically stressed rats, regardless of metyrapone treatment displayed more rearing in the open field when tested immediately after the completion of fear conditioning. These data support the hypothesis that increased emotionality and enhanced fear conditioning exhibited by chronically stressed rats may be due to endogenous corticosterone secretion at the time of fear conditioned training. Moreover, these data suggest that chronic stress impairs hippocampal-dependent processes more robustly than hippocampal-independent processes after metyrapone to reduce corticosterone secretion during aversive training.

Short CommunicationChronic stress leaves novelty-seeking behavior intact while impairing spatial recognition memory in the Y-maze

“…Body weight gain was analyzed because previous studies have shown that chronic stress reduces weight gain in male rats (Conrad et al 2001, Magariños and McEwen 1995, Watanabe et al 1992. A 2 ×4 repeated measures ANOVA for stress treatment (control & stress) and day (1, 7, 14 & 21) revealed a significant main effect for stress, F(1, 32) = 35.49, p < 0.001, a significant main effect for day, F(3, 96) = 746.86, p < 0.001, and a significant interaction between stress and day, F(3, 96) = 141.20, p < 0.001, showing that stressed rats gained weight more slowly than controls over three weeks of restraint (Control d1 329.6 ± 4.29, d21 449.2 ± 5.49; Stress d1 342.6 ± 3.29, d21 385.5 ± 3.5).…”

Chronic Stress- and Sex-Specific Neuromorphological and Functional Changes in Limbic Structures

“…The amygdala is necessary for acquisition of fear conditioning [22,248], which is enhanced by chronic stress in males [23,249] or GC [24]. Similarly, chronic stress enhances dendritic arborization in the amygdala of males [117,123,250], a mechanism that may contribute to enhanced acquisition of fear conditioning.…”

Chronic stress enhances spatial memory in ovariectomized female rats despite CA3 dendritic retraction: Possible involvement of CA1 neurons

“…Although CA3 dendritic retraction is associated with memory deficits in males, chronically-stressed male rats exhibit increased hippocampal-dependent contextual fear conditioning compared with controls, despite CA3 dendritic retraction (Conrad et al, 1999(Conrad et al, , 2001). In addition, inhibiting CORT synthesis with metyrapone on the day of training prevents stress-induced spatial memory deficits when dendritic retraction should be present (Wright et al, 2004).…”