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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

Freezing behavior from contextual fear conditioning testing beginning 7 days following stress and/or mTBI, including (A) response to footshock during fear conditioning acquisition day and (B) response to context during the three test days in 1 min time bins, each 8 min test separated by 24 h (as indicated by the gray dashed vertical lines).∗ Indicates significant difference from the control + sham group, while the symbol # indicates significant difference between the social defeat with mTBI vs. all other groups (p < 0.05).
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Figure 3: Freezing behavior from contextual fear conditioning testing beginning 7 days following stress and/or mTBI, including (A) response to footshock during fear conditioning acquisition day and (B) response to context during the three test days in 1 min time bins, each 8 min test separated by 24 h (as indicated by the gray dashed vertical lines).∗ Indicates significant difference from the control + sham group, while the symbol # indicates significant difference between the social defeat with mTBI vs. all other groups (p < 0.05).

Mentions: Unconditioned freezing duration in response to foot shock was not different between groups [Figure 3A; F(3,41) = 0.229, p = 0.876]. In contrast, two way ANOVA across the three testing sessions revealed a significant main effect of treatment [Figure 3B; F(3,40) = 13.706, p < 0.001], a significant main effect of time [Figure 3B; F(23,918) = 29.029, p < 0.001] and a significant interaction between treatment and time [Figure 3B; F(69,918) = 2.426, p < 0.001] for freezing behavior. All treatment groups (mTBI alone, social defeat alone, and the combined social defeat + mTBI) exhibited more freezing compared to the control + sham group the first test day (SNK, p < 0.05 for all eight time bins on test day 1; Figure 3B). However, only the combined social defeat + mTBI group showed increased freezing compare to controls during test day 2 (SNK, p < 0.05 for all eight time bins on test day 2; Figure 3B) and test day 3 (SNK, p < 0.05 for the first four time bins on test day 3; Figure 3B).


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)

Freezing behavior from contextual fear conditioning testing beginning 7 days following stress and/or mTBI, including (A) response to footshock during fear conditioning acquisition day and (B) response to context during the three test days in 1 min time bins, each 8 min test separated by 24 h (as indicated by the gray dashed vertical lines).∗ Indicates significant difference from the control + sham group, while the symbol # indicates significant difference between the social defeat with mTBI vs. all other groups (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Freezing behavior from contextual fear conditioning testing beginning 7 days following stress and/or mTBI, including (A) response to footshock during fear conditioning acquisition day and (B) response to context during the three test days in 1 min time bins, each 8 min test separated by 24 h (as indicated by the gray dashed vertical lines).∗ Indicates significant difference from the control + sham group, while the symbol # indicates significant difference between the social defeat with mTBI vs. all other groups (p < 0.05).
Mentions: Unconditioned freezing duration in response to foot shock was not different between groups [Figure 3A; F(3,41) = 0.229, p = 0.876]. In contrast, two way ANOVA across the three testing sessions revealed a significant main effect of treatment [Figure 3B; F(3,40) = 13.706, p < 0.001], a significant main effect of time [Figure 3B; F(23,918) = 29.029, p < 0.001] and a significant interaction between treatment and time [Figure 3B; F(69,918) = 2.426, p < 0.001] for freezing behavior. All treatment groups (mTBI alone, social defeat alone, and the combined social defeat + mTBI) exhibited more freezing compared to the control + sham group the first test day (SNK, p < 0.05 for all eight time bins on test day 1; Figure 3B). However, only the combined social defeat + mTBI group showed increased freezing compare to controls during test day 2 (SNK, p < 0.05 for all eight time bins on test day 2; Figure 3B) and test day 3 (SNK, p < 0.05 for the first four time bins on test day 3; Figure 3B).

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