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Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats.

Davies DR, Olson D, Meyer DL, Scholl JL, Watt MJ, Manzerra P, Renner KJ, Forster GL - Front Behav Neurosci (2016)

Bottom Line: However, this effect was enhanced by the combination of treatments.Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning.The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota Vermillion, SD, USA.

ABSTRACT
Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

No MeSH data available.


Related in: MedlinePlus

Behavioral measures from EPM testing 6 days following stress and/or mTBI, including (A) total number of entries into open arms, (B) total time spent in open arms and (C) total distance moved during testing.∗ Overlying a bar indicates significant difference between individual groups (p < 0.05).
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Figure 2: Behavioral measures from EPM testing 6 days following stress and/or mTBI, including (A) total number of entries into open arms, (B) total time spent in open arms and (C) total distance moved during testing.∗ Overlying a bar indicates significant difference between individual groups (p < 0.05).

Mentions: Both social defeat and mTBI independently affected the number of entries [Figure 2A; F(3,36)= 3.296, p = 0.031] and time spent in open arms of the EPM [Figure 2B; F(3,33)= 10.331, p < 0.001]. Rats exposed to social defeat in the absence of mTBI (social defeat + sham) made significantly fewer open arm entries (Figure 2A) and spent less time in the open arms (Figure 2B), than controls that received sham surgeries (SNK, p < 0.05 for both comparisons). Similarly, mTBI treatment in control-handled rats was sufficient to reduce both open arm entry (Figure 2A) and duration (Figure 2B) compared to sham controls (SNK, p < 0.05). Social defeat on its own had equivalent effects to mTBI only, with no difference in either number of entries (Figure 2A) or time spent in open arms (Figure 2B) between social defeat + sham and control + mTBI groups (SNK, p > 0.05). However, the combination of social defeat with mTBI had the greatest effect on anxiety-like behavior, reducing the number of open arm entries not only compared to control + sham treatment but also in comparison to both defeat alone or mTBI alone (Figure 2A, SNK, p < 0.05 for all comparisons). Likewise, the time spent in open arms was significantly reduced in rats that received both social defeat and mTBI compared with all other groups (Figure 2B, SNK, p < 0.05 for all comparisons). No difference existed among treatment groups in total distance moved during the EPM test [Figure 2C; F(3,36) = 1.004, p = 0.402].


Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats.

Davies DR, Olson D, Meyer DL, Scholl JL, Watt MJ, Manzerra P, Renner KJ, Forster GL - Front Behav Neurosci (2016)

Behavioral measures from EPM testing 6 days following stress and/or mTBI, including (A) total number of entries into open arms, (B) total time spent in open arms and (C) total distance moved during testing.∗ Overlying a bar indicates significant difference between individual groups (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835499&req=5

Figure 2: Behavioral measures from EPM testing 6 days following stress and/or mTBI, including (A) total number of entries into open arms, (B) total time spent in open arms and (C) total distance moved during testing.∗ Overlying a bar indicates significant difference between individual groups (p < 0.05).
Mentions: Both social defeat and mTBI independently affected the number of entries [Figure 2A; F(3,36)= 3.296, p = 0.031] and time spent in open arms of the EPM [Figure 2B; F(3,33)= 10.331, p < 0.001]. Rats exposed to social defeat in the absence of mTBI (social defeat + sham) made significantly fewer open arm entries (Figure 2A) and spent less time in the open arms (Figure 2B), than controls that received sham surgeries (SNK, p < 0.05 for both comparisons). Similarly, mTBI treatment in control-handled rats was sufficient to reduce both open arm entry (Figure 2A) and duration (Figure 2B) compared to sham controls (SNK, p < 0.05). Social defeat on its own had equivalent effects to mTBI only, with no difference in either number of entries (Figure 2A) or time spent in open arms (Figure 2B) between social defeat + sham and control + mTBI groups (SNK, p > 0.05). However, the combination of social defeat with mTBI had the greatest effect on anxiety-like behavior, reducing the number of open arm entries not only compared to control + sham treatment but also in comparison to both defeat alone or mTBI alone (Figure 2A, SNK, p < 0.05 for all comparisons). Likewise, the time spent in open arms was significantly reduced in rats that received both social defeat and mTBI compared with all other groups (Figure 2B, SNK, p < 0.05 for all comparisons). No difference existed among treatment groups in total distance moved during the EPM test [Figure 2C; F(3,36) = 1.004, p = 0.402].

Bottom Line: However, this effect was enhanced by the combination of treatments.Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning.The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

View Article: PubMed Central - PubMed

Affiliation: Center for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota Vermillion, SD, USA.

ABSTRACT
Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

No MeSH data available.


Related in: MedlinePlus