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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

Catecholamine meatsurements 7 days following stress and/or mTBI, including (A) dopamine (DA) concentrations in the dorsal hippocampus, (B) dopamine concentrations in the ventral hippocampus, (C) epinephrine (Epi) concentrations in the medial amygdala, (D) epinephrine concentrations in the dorsal raphe nucleus, and (E) norepinephrine concentrations in the central amygdala.∗ indicates significant difference from all other groups, while ∗ overlying a bar indicates significant difference between individual groups (p < 0.05).
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Figure 5: Catecholamine meatsurements 7 days following stress and/or mTBI, including (A) dopamine (DA) concentrations in the dorsal hippocampus, (B) dopamine concentrations in the ventral hippocampus, (C) epinephrine (Epi) concentrations in the medial amygdala, (D) epinephrine concentrations in the dorsal raphe nucleus, and (E) norepinephrine concentrations in the central amygdala.∗ indicates significant difference from all other groups, while ∗ overlying a bar indicates significant difference between individual groups (p < 0.05).

Mentions: There was a high degree of overlap between regions showing alterations to serotonergic function and those in which catecholamine concentrations were affected. Changes to dopamine concentrations were only seen in the dorsal [Figure 5A; F(3,39) = 4.758, p = 0.006] and ventral hippocampus [Figure 5B; F(3,34) = 4.404, p = 0.01]. Increases in dorsal hippocampus dopamine concentrations were elicited only by the combination of social defeat and mTBI in comparison to all other groups (SNK, p = 0.023), while in the ventral hippocampus, only mTBI on its own caused an increase in dopamine relative to the other groups (SNK, p = 0.047). Epinephrine in the medial amygdala was differentially altered by treatment [Figure 5C; F(3,39) = 4.360, p = 0.010], with epinephrine concentrations significantly higher in the control + mTBI group when compared to control + sham (p = 0.008) and social defeat + mTBI (p = 0.041) groups, but not when compared to the social defeat + sham group (p = 0.156). The concentration of epinephrine was also significantly different in the dorsal raphe nucleus among treatment groups [Figure 5D; F(3,43) = 4.354, p = 0.009], with all treatments causing reductions in dorsal raphe epinephrine as compared to the control + sham group (SNK, p = 0.036). Finally, there was a significant difference among groups in norepinephrine concentration (pg/μg) in the central amygdala [Figure 5E; F(3,42) = 6.554, p = 0.001], with the social defeat + mTBI group exhibiting higher norepinephrine concentrations than all other groups (SNK, p-range = 0.001–0.033). There were no differences in either dopamine activity (DOPAC/DA) or DOPAC concentrations in any brain region examined (Table 2).


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)

Catecholamine meatsurements 7 days following stress and/or mTBI, including (A) dopamine (DA) concentrations in the dorsal hippocampus, (B) dopamine concentrations in the ventral hippocampus, (C) epinephrine (Epi) concentrations in the medial amygdala, (D) epinephrine concentrations in the dorsal raphe nucleus, and (E) norepinephrine concentrations in the central amygdala.∗ indicates significant difference from all other groups, while ∗ overlying a bar indicates significant difference between individual groups (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Catecholamine meatsurements 7 days following stress and/or mTBI, including (A) dopamine (DA) concentrations in the dorsal hippocampus, (B) dopamine concentrations in the ventral hippocampus, (C) epinephrine (Epi) concentrations in the medial amygdala, (D) epinephrine concentrations in the dorsal raphe nucleus, and (E) norepinephrine concentrations in the central amygdala.∗ indicates significant difference from all other groups, while ∗ overlying a bar indicates significant difference between individual groups (p < 0.05).
Mentions: There was a high degree of overlap between regions showing alterations to serotonergic function and those in which catecholamine concentrations were affected. Changes to dopamine concentrations were only seen in the dorsal [Figure 5A; F(3,39) = 4.758, p = 0.006] and ventral hippocampus [Figure 5B; F(3,34) = 4.404, p = 0.01]. Increases in dorsal hippocampus dopamine concentrations were elicited only by the combination of social defeat and mTBI in comparison to all other groups (SNK, p = 0.023), while in the ventral hippocampus, only mTBI on its own caused an increase in dopamine relative to the other groups (SNK, p = 0.047). Epinephrine in the medial amygdala was differentially altered by treatment [Figure 5C; F(3,39) = 4.360, p = 0.010], with epinephrine concentrations significantly higher in the control + mTBI group when compared to control + sham (p = 0.008) and social defeat + mTBI (p = 0.041) groups, but not when compared to the social defeat + sham group (p = 0.156). The concentration of epinephrine was also significantly different in the dorsal raphe nucleus among treatment groups [Figure 5D; F(3,43) = 4.354, p = 0.009], with all treatments causing reductions in dorsal raphe epinephrine as compared to the control + sham group (SNK, p = 0.036). Finally, there was a significant difference among groups in norepinephrine concentration (pg/μg) in the central amygdala [Figure 5E; F(3,42) = 6.554, p = 0.001], with the social defeat + mTBI group exhibiting higher norepinephrine concentrations than all other groups (SNK, p-range = 0.001–0.033). There were no differences in either dopamine activity (DOPAC/DA) or DOPAC concentrations in any brain region examined (Table 2).

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