Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.
BACKGROUND
Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development, are a significant risk factor for later life anxiety disorders such as posttraumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD, such as enhanced fear and anxiety. Here, we used a fear conditioning procedure in juvenile rats before maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD-related symptoms.


METHODS
Nineteen-day old rats were exposed to unpredictable and inescapable footshocks, and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning or elevated plus maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid and neuropeptide Y receptors.


RESULTS
Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear-related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar glucocorticoid receptors, decreased time spent in the open arm of an elevated plus maze, and an odor aversion associated with early-life footshocks.


CONCLUSIONS
These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD, even if there is no explicit memory of the early trauma.
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California; UCLA Behavioral Testing Core, Brain Research Institute, Los Angeles, Los Angeles, California. Electronic address: apoulos@ucla.edu.
Andrew M
AM
Poulos
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California; UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, Los Angeles, Los Angeles, California.
Maxine
M
Reger
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California.
Nehali
N
Mehta
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California; UCLA Behavioral Testing Core, Brain Research Institute, Los Angeles, Los Angeles, California.
Irina
I
Zhuravka
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California.
Sarah S
SS
Sterlace
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California.
Camille
C
Gannam
UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, Los Angeles, Los Angeles, California.
David A
DA
Hovda
UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, Los Angeles, Los Angeles, California; Department of Pediatrics, Division of Pediatric Neurology, Mattel Children's Hospital, Los Angeles, Los Angeles, California.
Christopher C
CC
Giza
Department of Psychology, Brain Research Institute, Los Angeles, Los Angeles, California; UCLA Behavioral Testing Core, Brain Research Institute, Los Angeles, Los Angeles, California; Department of Psychiatry and Biobehavioral Sciences, UCLA Integrative Center for Learning and Memory, Los Angeles, Los Angeles, California; Department of Medical and Molecular Pharmacology, University of California, Los Angeles, Los Angeles, California.
Michael S
MS
Fanselow
D000375:Aging; D000647:Amnesia / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004597:Electroshock; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D055696:Olfactory Perception / Q000502:physiology; D017440:Photoperiod; D020318:Rats, Long-Evans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology; D013315:Stress, Psychological / Q000503:physiopathology; D035501:Uncertainty
C066211:Npy1r protein, rat; D043562:Receptors, G-Protein-Coupled; D011965:Receptors, Glucocorticoid; D018013:Receptors, Neuropeptide; D003345:Corticosterone
Amnesia; development; early life stress; fear conditioning; hippocampus; rat