Environmental Enrichment Induces Behavioral Recovery and Enhanced Hippocampal Cell Proliferation in an Antidepressant-Resistant Animal Model for PTSD

Hendriksen, Erik; Prins, Jolanda; Olivier, Berend; Oosting, Ronald S.

doi:10.1371/journal.pone.0011943

Cited by 66 publications

(60 citation statements)

References 53 publications

(71 reference statements)

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“…Once the animal entered in the dark compartment the door was closed and 10 shocks (0.86 mA) of 6 seconds duration in 10 minutes were given. The conditions of the IFS procedure were based in previous studies (Hendriksen et al, 2010;Hendriksen et al, 2012;van Dijken et al, 1993;van Dijken et al, 1992). Control animals remained 10 minutes in the dark compartment without receiving shocks.…”

Section: Inescapable Foot-shock (Ifs) Proceduresmentioning

confidence: 99%

“…Despite this, and to our knowledge, there are only two studies examining the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results (Hendriksen et al, 2010;Tsuda et al, 1986). Moreover, no studies have monitored the in vivo release of noradrenaline in the amygdala or determined the causal relationship between these changes of noradrenaline outflow and the alterations of behavior in animals exposed to traumatic stress.…”

Section: Introductionmentioning

confidence: 95%

“…Also, heightened heart rate reactivity to startling stimuli (loud tones) and larger skin conductance response to novel stimuli have been observed in PTSD patients (Pitman et al, 2012). In animal models, exaggerated acoustic startle response and reduced locomotor activity in a novel environment have been used as measures of hyperarousal after exposure to traumatic stressors (Hendriksen et al, 2010;Kinn Rød et al, 2012;Stam, 2007;van Dijken et al, 1992;Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…This paradigm induces both long-lasting conditioned and non-conditioned anxiety (Chen et al, 2012;Daviu et al, 2010;Hendriksen et al, 2010;Hendriksen et al, 2012;Kinn Rød et al, 2012;van Dijken et al, 1992). In particular, IFS procedure produces a reduction in the activity in unknown environments 7 days after exposure to the shock (Daviu et al, 2010;Hendriksen et al, 2010;van Dijken et al, 1993;van Dijken et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

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SummaryIncreased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure 1) on reactivity to novelty in an open-field (as an index of hyperarousal), and 2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86 mA, and 6 seconds per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD.

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Section: Inescapable Foot-shock (Ifs) Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

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“…Reduced locomotor activity in a novel environment over time in the open field may reflect improved information processing and reduced emotionality associated with enrichment (Crawley et al 1997). In rats, enrichment without wheel running has been shown to have anxiolytic effects upon exposure to an inescapable foot shock procedure and result in altered monoamine metabolism (Hendriksen et al 2010). Enrichment only also has effects on synaptic plasticity, such as increased dendritic complexity of young granule neurons (Beauquis et al 2010), enhanced arborization of cortical neurons (Ip et al 2002), and elevated synaptophysin levels in hippocampus and cortex (Lambert et al 2005).…”

mentioning

confidence: 99%

Running is the neurogenic and neurotrophic stimulus in environmental enrichment

Kobilo¹,

Liu²,

Gandhi³

et al. 2011

Learn. Mem.

345

253

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Environmental enrichment (EE) increases dentate gyrus (DG) neurogenesis and brain-derived neurotrophic factor (BDNF) levels. However, running is considered an element of EE. To dissociate effects of physical activity and enrichment on hippocampal neurogenesis and BDNF levels, young female C57Bl/6 mice were housed under control, running, enrichment, or enrichment plus running conditions, and injected with bromodeoxyuridine. Cell genesis was assessed after 12 d and differentiation was analyzed 1 mo later. In addition, locomotor activity in the open field and hippocampal mature BDNF peptide levels were measured. Open-field adaptation was improved in all groups, compared to controls, but more so with running. New cell proliferation, survival, neuron number, and neurotrophin levels were enhanced only when running was accessible. We conclude that exercise is the critical factor mediating increased BDNF levels and adult hippocampal neurogenesis.[Supplemental material is available for this article.]Exposure to environmental enrichment (EE) has positive effects on brain function, including increased numbers of dendritic branches and spines, enlargement of synapses, and improved cognition (Bennett et al. 1964;Rosenzweig and Bennett 1996). More recently, it was discovered that EE enhances the survival of newly born neurons in the dentate gyrus (DG) of the hippocampus (Kempermann et al. 1997) and increases brain-derived neurotrophic factor (BDNF) levels (Falkenberg et al. 1992;Rossi et al. 2006;Sun et al. 2010). EE has many aspects, including increased opportunity for learning, socialization, and physical activity. Among these, exercise was found to enhance neurogenesis (van Praag et al. 1999). Subsequently, physical activity and enrichment have been regarded as equivalent neurogenic stimuli, albeit with different underlying mechanisms. Exercise is considered to mainly enhance cell proliferation, whereas enrichment is deemed to increase new cell survival (Olson et al. 2006;Kempermann et al. 2010). However, in many studies the enriched environment includes physical activity (Kempermann et al. 1997(Kempermann et al. , 1998van Praag et al. 1999;Rossi et al. 2006;Schloesser et al. 2010;Sun et al. 2010), making it difficult to assess the unique contributions of EE and exercise to adult neurogenesis, neurotrophin levels, and behavior.The current study aims to directly differentiate between the effects of enriched environment only (EEO), physical activity (RUN), and the combination of enrichment and running (EER). Here we show that running is the critical factor in stimulating adult hippocampal neurogenesis and enhancing mature BDNF peptide levels. Moreover, enrichment in the absence of running does not increase adult hippocampal neurogenesis or BDNF levels in the hippocampus. Open-field adaptation was improved in all groups as compared to controls, but more so in the groups that included running. These findings suggest that enrichment and exercise are distinct functional interventions.Forty female C57B1/6 mice (5 wk old) were div...

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Effect of Forced and Voluntary Exercise on Neural Plasticity Mediated by Astrocytes

Bernardi

Brauner

Gonçalves

2015

Diet and Exercise in Cognitive Function and Neurological Diseases

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Environmental Enrichment Induces Behavioral Recovery and Enhanced Hippocampal Cell Proliferation in an Antidepressant-Resistant Animal Model for PTSD

Cited by 66 publications

References 53 publications

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Running is the neurogenic and neurotrophic stimulus in environmental enrichment

Effect of Forced and Voluntary Exercise on Neural Plasticity Mediated by Astrocytes

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