Sensitization of fear learning to mild unconditional stimuli in male and female rats.

Stress-enhanced fear learning (SEFL) refers to the long-lasting nonassociative sensitization produced by intense stress (e.g., repeated and unpredictable footshock) that results in increased fear learning to a mild conditioning regimen (e.g., one shock). SEFL experiments suggest that one component of posttraumatic behavior is inappropriately strong fear conditioning occurring to relatively mild stressors. Past reports of SEFL have used the same intensity (1 mA) of footshock to cause both the sensitization and conditioning of new fear. SEFL would be a particularly problematic component of posttrauma behavior if intense stress results in substantial fear conditioning under conditions that would not normally support conditioning. Therefore, we determined if SEFL occurred when the conditioning shock was substantially milder than the SEFL-inducing shock. The results indicate that exposure to a sensitizing regimen of shock can convert a mild footshock that normally does not support measurable levels of fear conditioning into one that causes substantial learned fear. Moreover, as the intensity of single footshock increases, so does the capacity of the prior stressor to contribute to the sensitization of fear responses. Consistent with prior studies, males acquired and retained a greater level of fear conditioning than female rats, however the level of sensitization did not differ between sexes

Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats.

BackgroundTraumatic 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.MethodsNineteen-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.ResultsEarly 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.ConclusionsThese 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