Effects of mild TBI from repeated blast overpressure on the expression and extinction of conditioned fear in rats.
Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are pressing medical issues for the Warfighter. Symptoms of mTBI can overlap with those of PTSD, suggesting the possibility of a causal or mediating role of mTBI in PTSD. To address whether mTBI can exacerbate the neurobiological processes associated with traumatic stress, we evaluated the impact of mTBI from a blast overpressure (BOP) on the expression of a conditioned fear. In the rat, conditioned fear models are used to evaluate the emotional conditioning processes that are known to become dysfunctional in PTSD. Rats were first trained on a variable interval (VI), food maintained, operant conditioning task that established a general measure of performance. Inescapable electric shock (IES) was paired with an audio-visual conditioned stimulus (CS) and followed 1day later by three daily exposures to BOP (75kPa). Subsequently, the CS alone was presented once every 7days for 2months, beginning 4days following the last BOP. The CS was presented during the VI sessions allowing a concurrent measure of performance. Treatment groups (n=10, each group) received IES+BOP, IES+sham-BOP, sham-IES+BOP or sham-IES+sham-BOP. As expected, pairing the CS with IES produced a robust conditioned fear that was quantified by a suppression of responding on the VI. BOP significantly decreased the expression of the conditioned fear. No systematic short- or long-term performance deficits were observed on the VI from BOP. These results show that mTBI from BOP can affect the expression of a conditioned fear and suggests that BOP caused a decrease in inhibitory behavioral control. Continued presentation of the CS produced progressively less response suppression in both fear conditioned treatments, consistent with extinction of the conditioned fear. Taken together, these results show that mTBI from BOP can affect the expression of a conditioned fear but not necessarily in a manner that increases the conditioned fear or extends the extinction process.
Behavioral Biology Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address: Raymond.Genovese@US.Army.Mil.
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Genovese
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Simmons
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Ahlers
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Maudlin-Jeronimo
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Dave
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Boutte
D000818:Animals; D001753:Blast Injuries / Q000503:physiopathology* / Q000523:psychology; D001930:Brain Injuries / Q000503:physiopathology* / Q000523:psychology; D003216:Conditioning, Operant / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D013997:Time Factors
ANOVA; BOP; CR; CS; IES; PTSD; VI; analysis of variance; blast overpressure; conditioned fear; conditioned response; conditioned stimulus; inescapable electric shock; mTBI; mild traumatic brain injury; operant conditioning; post-traumatic stress disorder; stress processes; variable interval (schedule of reinforcement)