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Biol Psychiatry. 2012 Feb 15;71(4):335-43. doi: 10.1016/j.biopsych.2011.11.007. Epub 2011 Dec 9.

Concussive brain injury enhances fear learning and excitatory processes in the amygdala.

Author information

1
UCLA Neurotrauma Laboratory, Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA.

Abstract

BACKGROUND:

Mild traumatic brain injury (cerebral concussion) results in cognitive and emotional dysfunction. These injuries are a significant risk factor for the development of anxiety disorders, including posttraumatic stress disorder. However, because physically traumatic events typically occur in a highly emotional context, it is unknown whether traumatic brain injury itself is a cause of augmented fear and anxiety.

METHODS:

Rats were trained with one of five fear-conditioning procedures (n = 105) 2 days after concussive brain trauma. Fear learning was assessed over subsequent days and chronic changes in fear learning and memory circuitry were assessed by measuring N-methyl-D-aspartate receptor subunits and glutamic acid decarboxylase, 67 kDa isoform protein levels in the hippocampus and basolateral amygdala complex (BLA).

RESULTS:

Injured rats exhibited an overall increase in fear conditioning, regardless of whether fear was retrieved via discrete or contextual-spatial stimuli. Moreover, injured rats appeared to overgeneralize learned fear to both conditioned and novel stimuli. Although no gross histopathology was evident, injury resulted in a significant upregulation of excitatory N-methyl-D-aspartate receptors in the BLA. There was a trend toward decreased γ-aminobutyric acid-related inhibition (glutamic acid decarboxylase, 67 kDa isoform) in the BLA and hippocampus.

CONCLUSIONS:

These results suggest that mild traumatic brain injury predisposes the brain toward heightened fear learning during stressful postinjury events and provides a potential molecular mechanism by which this occurs. Furthermore, these data represent a novel rodent model that can help advance the neurobiological and therapeutic understanding of the comorbidity of posttraumatic stress disorder and traumatic brain injury.

PMID:
22169439
PMCID:
PMC3264758
DOI:
10.1016/j.biopsych.2011.11.007
[Indexed for MEDLINE]
Free PMC Article

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