Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress.

Fear promotes adaptive responses to threats. However, when the level of fear is not proportional to the level of threat, maladaptive fear-related behaviors characteristic of anxiety disorders result. Post-traumatic stress disorder develops in response to a traumatic event, and patients often show sensitized reactions to mild stressors associated with the trauma. Stress-enhanced fear learning (SEFL) is a rodent model of this sensitized responding, in which exposure to a 15-shock stressor nonassociatively enhances subsequent fear conditioning training with only a single trial. We examined the role of corticosterone (CORT) in SEFL. Administration of the CORT synthesis blocker metyrapone prior to the stressor, but not at time points after, attenuated SEFL. Moreover, CORT co-administered with metyrapone rescued SEFL. However, CORT alone without the stressor was not sufficient to produce SEFL. In these same animals, we then looked for correlates of SEFL in terms of changes in excitatory receptor expression. Western blot analysis of the basolateral amygdala (BLA) revealed an increase in the GluA1 AMPA receptor subunit that correlated with SEFL. Thus, CORT is permissive to trauma-induced changes in BLA function.

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.

Stress increases voluntary alcohol intake, but does not alter established drinking habits in a rat model of posttraumatic stress disorder.

BACKGROUND: Life-altering anxiety disorders, such as posttraumatic stress disorder (PTSD), can co-occur at high rates with substance use disorders. Alcoholism, compared with other substance use disorders, is particularly common. Rodent studies of acute stress effects on alcohol consumption show that stress can alter ethanol (EtOH) consumption. This study examined voluntary EtOH consumption in male Long-Evans rats that had undergone a stress-enhanced fear learning (SEFL) procedure. METHODS: Adult Long-Evans rats were exposed to a stress that consisted of 15 inescapable foot-shocks (1 mA, 1 second) known to cause a long-lasting nonassociative enhancement of subsequent fear learning. Control animals received no shock. One day later, animals were placed in a novel and very different context and received a single foot-shock. On day 3, animals were returned to the single shock context and freezing was used as a measure of learned fear. The intermittent access 2-bottle choice (2BC) regimen consisted of 1 bottle of water and 1 bottle of experimental solution, either 19% EtOH or 28.4% sucrose-0.08% quinine, for a 24-hour period, 3 days a week, and all other times 2 water bottles. This regimen lasted until stable levels of experimental solution drinking were reached, at which point the experimental solution was removed for 40 days and then returned to measure the resumption of consumption. RESULTS: Rats that received stress prior to EtOH consumed significantly more EtOH than control rats before and after reinstatement. Rats that received stress after drinking was established did not consume significantly more EtOH when the drug was returned. Stress had no significant effect on sucrose-quinine drinking, our calorie and taste control for EtOH. CONCLUSIONS: A single traumatic event sufficient to produce long-lasting enhancement of fear learning increases voluntary EtOH consumption, but does not alter previously acquired EtOH drinking habits or alter the consumption of a calorically equivalent sweet-bitter-tasting solution.

Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction.

Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24 h after stress. Recent studies found that extinction from 10 min to 1 h subsequent to fear conditioning "erased" learning, whereas later extinction, occurring from 24 to 72 h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial's procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10 min or 72 h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments.

Involuntary attention and brightness contrast.

Carrasco, Ling, and Read (2004) reported that involuntary attention increased perceived contrast. We replicated Carrasco et al. and then tested an alternative hypothesis: With stimuli near threshold, a peripheral cue biased observers to believe a stimulus had been presented in the cued location. Consistent with this hypothesis, the effect disappeared when we used higher-contrast stimuli. We further tested the guessing-bias hypothesis in three ways: (1) In a detection experiment, the cue affected bias, but did not increase d'; (2) when the cue followed the stimulus, we obtained the same results as when the cue preceded the stimulus; (3) in one experiment, some trials contained no stimulus, yet observers responded that the cued blank stimulus had higher contrast than the uncued blank stimulus. The results suggest that the effects of a noninformative peripheral cue are best described in terms of nonperceptual biases.