Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior

Vyas, Ajai; Pillai, Anup G.; Chattarji, Sumantra

doi:10.1016/j.neuroscience.2004.07.013

Cited by 406 publications

(353 citation statements)

References 25 publications

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“…Moreover, there was a significant (po0.003) rightward shift in the cumulative frequency plot for the stress + vehicle neurons compared to control + vehicle neurons, indicating that the observed dendritic hypertrophy was present across a wide range of total dendritic length values for all the BLA neurons analyzed (Figure 4b). Taken together, these data from vehicleinjected animals are consistent with previous reports on stress-induced dendritic growth in BLA principal neurons (Vyas et al, 2002(Vyas et al, , 2004.…”

Section: Tianeptine Blocks Chronic Stress-induced Dendritic Hypertropsupporting

confidence: 92%

“…NMDARs play a central role in amygdalar LTP and fear memory formation, and chronic tianeptine treatment before acquisition of fear conditioning inhibits subsequent recall of the fear memory (Burghardt et al, 2004). Further, exposure to stress facilitates various forms of classical fear conditioning and anxiety in rats (Shors and Mathew, 1998;Vyas et al, 2004). Conversely, local infusion of NMDAR antagonists into the BLA prevents these facilitatory effects of stress (Shors and Mathew, 1998).…”

Section: Discussionmentioning

confidence: 99%

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The Same Antidepressant Elicits Contrasting Patterns of Synaptic Changes in the Amygdala vs Hippocampus

Pillai

Anilkumar

Chattarji

2012

Neuropsychopharmacol

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As depression-like symptoms are often precipitated by some form of stress, animal models of stress have been used extensively to investigate cellular mechanisms of depression. Despite being implicated in the emotional symptoms of depression, the amygdala has received little attention compared to the hippocampus in the past studies of antidepressant action. Further, these investigations have not taken into account the contrasting effects of chronic stress on the hippocampus vs amygdala. If an antidepressant is to be equally effective in countering the differential effects of stress on both brain areas, then it is faced with the challenge of eliciting contrasting effects in these two structures. We tested this prediction by examining the impact of tianeptine, an antidepressant with proven clinical efficacy, on neurons of the lateral amygdala (LA) and hippocampal area CA1. Tianeptine reduces N-methyl-D-aspartate (NMDA)-receptor-mediated synaptic currents, without affecting a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) currents, in LA neurons. By contrast, tianeptine enhances both NMDA and AMPA currents in area CA1. Tianeptine also lowers action potential firing in LA neurons. As tianeptine modulates cellular metrics that, in addition to mediating amygdalar behavioral output, are also affected by stress, we tested if tianeptine succeeds in countering stress effects in the intact animal. We find that tianeptine prevents two important functional consequences of chronic stress-induced plasticity in the amygdalaFdendritic growth and enhanced anxiety-like behavior. These results provide evidence for antidepressant action on amygdalar neurons that are not only distinct from the hippocampus, but also protect against the debilitating impact of stress on amygdalar structure and function.

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Section: Tianeptine Blocks Chronic Stress-induced Dendritic Hypertropsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

The Same Antidepressant Elicits Contrasting Patterns of Synaptic Changes in the Amygdala vs Hippocampus

Pillai

Anilkumar

Chattarji

2012

Neuropsychopharmacol

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“…Of particular interest would be to understand how chronic unpredictable stress alters brain regions and neurotransmitters thought to participate in stress activation and anxiety behaviors. Previous studies have found that structural remodeling of neurons in the dorsal hippocampus and basolateral amygdala persists for 3 weeks following termination of chronic restraint stress, as does increased anxietylike behaviors [7,31,57,59]. Unpredictable stress exposure did not result in similar structural or immediate behavioral changes, which may suggest that different neural substrates mediate the increase in anxiety behaviors following predictable compared to unpredictable stress [57,58].…”

Section: Discussionmentioning

confidence: 92%

“…Although the unpredictable stress procedures have been suggested as appropriate animal models of anxiety disorders due to their behavioral effects, these behavioral effects have not been measured after the cessation of the stress procedure [14,58]. Previous research with chronic predictable or single stress exposure reported an increase in anxiety measures 1-3 weeks following the last stress exposure [4,7,19,30,32,54,55,59]. Therefore, to systematically investigate the delayed effects of chronic unpredictable stress (CUS), the current study exposed rats to 10 days of unpredictable stress and then assessed anxiety on several behavioral measures 1, 7 or 14 days following the last stress exposure.…”

Section: Introductionmentioning

confidence: 99%

The delayed effects of chronic unpredictable stress on anxiety measures

Matuszewich

Karney

Carter

et al. 2007

Physiology & Behavior

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Previous research has found that exposure to unpredictable stress can augment anxiety in humans and animals. The appearance of anxiety symptoms in humans frequently develop after stress exposure has terminated, but few rodent studies have systematically examined the delayed anxiogenic effects of unpredictable stress. Therefore, the current study investigated whether anxiety-like behaviors in rats would increase at several time intervals following exposure to chronic unpredictable stress (CUS). Unconditioned and conditioned response tasks were used to assess anxiety in male rats 1, 7 or 14 days following exposure to 10 days of a variety of stressors. Rats exposed to CUS showed increased burying behaviors and immobility during the defensive burying test, a conditioned anxiety test. The effects on burying behavior were apparent 7 and 14 days after the termination of the unpredictable stress procedure, but not when tested 1 day after CUS. Total time immobile in the defensive burying test also increased 14 days after termination of the last stressor. In contrast, there were no significant effects of CUS on behavioral measures in the unconditioned response tasks, the elevated plus-maze or light-dark box, at any time point following exposure to CUS. The current findings suggest that CUS may be a useful model of human conditioned anxiety that develops subsequent to chronic stress exposure.

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“…This difference is reflected by a faster reactivity of the structural features of the amygdala to the effects of stress exposure; 10 days of immobilization stress was shown to be sufficient to induce dendritic hypertrophy and spine formation in the basolateral amygdala (Mitra et al, 2005). Additionally, the difference is reflected by a slower ability of the amygdala to recover from chronic stress; even after 21 days of stress-free recovery from a previous chronic immobilization stress, a persistent increase in dendritic arborization in the basolateral amygdala spiny neurons was observed, whereas hippocampal CA3 atrophy had completely recovered by this time point (Vyas et al, 2004). Only a 10-day stress-free period was sufficient to reverse hippocampal CA3 atrophy (Conrad et al, 1999).…”

Section: Discussionmentioning

confidence: 97%

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Castro

Diessler

Varea

et al. 2012

Psychoneuroendocrinology

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Summary Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depressionlike behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activityas measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) -in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in

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Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior

Cited by 406 publications

References 25 publications

The Same Antidepressant Elicits Contrasting Patterns of Synaptic Changes in the Amygdala vs Hippocampus

The Same Antidepressant Elicits Contrasting Patterns of Synaptic Changes in the Amygdala vs Hippocampus

The delayed effects of chronic unpredictable stress on anxiety measures

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

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