Predator-based psychosocial stress model of PTSD differentially influences voluntary ethanol consumption depending on methodology.

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder typified by diagnostic symptom clusters including hyperarousal, avoidance, negative cognitions and mood, and intrusive re-experiencing of the traumatic event. Patients with PTSD have been reported to self-medicate with alcohol to ameliorate hyperarousal symptoms associated with the disorder. Research utilizing rodent models of PTSD to emulate this behavioral phenomenon has thus far yielded inconsistent results. In the present study, we examined the effects of a predator-based psychosocial stress model of PTSD on voluntary ethanol consumption. In the first of two experiments, following exposure to a 31-day stress or control paradigm, rats were singly housed during the dark cycle with free access to 1% sucrose solution or 10% ethanol, which was also sweetened with 1% sucrose. Over the course of a 20-day period of ethanol access, stressed rats consumed significantly less ethanol than non-stressed rats. These counterintuitive results prompted the completion of a second experiment which was identical to the first, except rats were also exposed to the two-bottle paradigm for 20 days before the stress or control paradigm. In the second experiment, after the stress manipulation, stressed rats exhibited significantly greater ethanol preference than non-stressed rats. These findings suggest that prior exposure to ethanol influences the subsequent effect of stress on ethanol intake. They also validate the use of the present model of PTSD to examine potential mechanisms underlying stress-related changes in ethanol-seeking behavior.

Sex-dependent effects of sleep deprivation on myocardial sensitivity to ischemic injury.

Sleep deprivation is associated with increased risk of myocardial infarction. However, it is unknown whether the effects of sleep deprivation are limited to increasing the likelihood of experiencing a myocardial infarction or if sleep deprivation also increases the extent of myocardial injury. In this study, rats were deprived of paradoxical sleep for 96 h using the platform-over-water method. Control rats were subjected to the same condition except the control platform was large enough for the rats to sleep. Hearts from sleep deprived and control rats were subjected to 20 min ischemia on a Langendorff isolated heart system. Infarct size and post ischemic recovery of contractile function were unaffected by sleep deprivation in male hearts. In contrast, hearts from sleep-deprived females exhibited significantly larger infarcts than hearts from control females. Post ischemic recovery of rate pressure product and + dP/dT were significantly attenuated by sleep deprivation in female hearts, and post ischemic recovery of end diastolic pressure was significantly elevated in hearts from sleep deprived females compared to control females, indicating that post ischemic recovery of both systolic and diastolic function were worsened by sleep deprivation. These data provide evidence that sleep deprivation increases the extent of ischemia-induced injury in a sex-dependent manner.

Sex-dependent effects of chronic psychosocial stress on myocardial sensitivity to ischemic injury.

Individuals with post-traumatic stress disorder (PTSD) experience many debilitating symptoms, including intrusive memories, persistent anxiety and avoidance of trauma-related cues. PTSD also results in numerous physiological complications, including increased risk for cardiovascular disease (CVD). However, characterization of PTSD-induced cardiovascular alterations is lacking, especially in preclinical models of the disorder. Thus, we examined the impact of a psychosocial predator-based animal model of PTSD on myocardial sensitivity to ischemic injury. Male and female Sprague-Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures, separated by a period of 10 days, and were subjected to daily social instability throughout the paradigm. Control rats were handled daily for the duration of the experiment. Rats were tested on the elevated plus maze (EPM) on day 32, and hearts were isolated on day 33 and subjected to 20 min ischemia and 2 h reperfusion on a Langendorff isolated heart system. Stressed male and female rats gained less body weight relative to controls, but only stressed males exhibited increased anxiety on the EPM. Male, but not female, rats exposed to psychosocial stress exhibited significantly larger infarcts and attenuated post-ischemic recovery of contractile function compared to controls. Our data demonstrate that predator stress combined with daily social instability sex-dependently increases myocardial sensitivity to ischemic injury. Thus, this manipulation may be useful for studying potential mechanisms underlying cardiovascular alterations in PTSD, as well as sex differences in the cardiovascular stress response.