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animal model, corticosterone, forebrain, norepinephrine, PTSD
Abstract:
This study measured changes in brain extracellular norepinephrine (NE)
and free corticosterone (CORT) levels in a mouse model of post-traumatic
stress disorder and related them to hyperarousal and fear memory
retention. To this end, microdialysis in the medial prefrontal cortex
(mPFC) and the hippocampus (HPC) of male C57BL/6NCrl mice was performed
during an acoustic startleresponse (ASR) and following an electric foot
shock (FS), as well as during an ASR and recall of contextual fear (CF)
1day later. Changes in ASR-stimulated NE levels in the mPFC corresponded
to ASR 34days after FS. Changes in basal and ASR-stimulated
extracellular NE levels in the HPC, in contrast, were related to
expression of early (day 2) and late (day 34) CF after FS. The increase
in extracellular NE levels correlated in a U-shape manner with arousal
levels and CF, thus suggesting a non-direct relationship. Stress of
different modalities/strength (ASR, FS and CF) caused a similar relative
increase in free CORT levels both in the mPFC and the HPC. One day after
FS, ASR-induced increases in the CORT content in the mPFC tended to
correlate with the FS-potentiated ASR in a U-shape manner. Taken
together, these data show that the intracerebral increase in free CORT
was likely related to an immediate response to stress, whereas NE
neurotransmission in the forebrain predicted arousal and CF 1month after
trauma.
