Protective effect of propranolol and nadolol on social defeat-induced behavioral impairments in rats.

Benzodiazepines and SSRIs are considered as standard treatment options for anxiety and depression, hallmarks of Post-Traumatic Stress Disorder (PTSD), although their use is often limited by adverse effects. While promising evidence emerged with ß-adrenergic receptor (ß-AR) antagonists (or 'ß-blockers') and PTSD relief, efficacy issues dampened the excitement. However, we believe it is premature to completely eliminate a beneficial role of ß-blockers. Our previous work has suggested that social defeat (SD) results in anxiety-like and depression-like behaviors in rats. Here, using the SD paradigm, we examined the effect of several ß-adrenergic receptor antagonists (propranolol, nadolol, bisoprolol) on these behaviors in rats. Following acclimatization, Sprague-Dawley rats received no treatment (for control groups) or treated with ; propranolol (50 mg/kg/day in water), or nadolol (18 mg/kg/day in rats' chow), or bisoprolol (15 mg/kg/day in water). The treatment lasted for 36 days, following which rats were subjected to SD/control exposures (1 week). Later, anxiety-like and depression-like behaviors, social interaction and learning-memory function tests were conducted. SD rats exhibited anxiety- and depression-like behavior as well as learning-memory impairment. Propranolol and nadolol protected SD rats from exhibiting anxiety-or depression-like behaviors. Bisoprolol treatment did not mitigate SD-induced behavioral impairments in rats. Nadolol, propranolol or bisoprolol have no effect in attenuating SD-induced memory function tests. These results suggest that certain 'ß-blockers' have the potential to mitigate the negative psychological effects of traumatic events.

Prior treadmill exercise promotes resilience to vicarious trauma in rats.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a serious psychological condition, which can develop both from physically experiencing and also from witnessing traumatic events. There is evidence that physical exercise can have a positive impact on the symptoms of PTSD. Relevant to this, in our previous pre-clinical work, beneficial effects of treadmill exercise were reported on PTSD-like behaviors in a social defeat paradigm, a rat model of direct physical trauma. However, the role of exercise on vicariously acquired PTSD-like phenotype was not examined. OBJECTIVE: In this study, we utilized a rodent PTSD model, which mimics both the physical as well as the witness experience of trauma, and examined the impact of moderate treadmill exercise in mitigating vicariously acquired PTSD-like behaviors in rats. METHODS: Our PTSD model is a modified social defeat paradigm, which involves aggressive encounters between a large Long-Evans male rat (resident) and a smaller Sprague-Dawley male rat (intruder), resulting in intruder social defeat. The cage mate of the intruder is positioned to witness intruder defeat. Rats were grouped as control (CON), social defeat (SD), exercise (EX), trauma witness (TW), and exercise prior to trauma witness (EX-TW). After acclimatization for 7days, the exercised groups were subjected to a daily 30-min treadmill exercise regimen for 14days. On day 21, the SD group was exposed for 7days of social defeat, while the TW groups witnessed social defeat. On days 28-34, behavioral and cognitive tests including short-term (STM) and long-term (LTM) memory function, anxiety- and depression-like behaviors were conducted. RESULTS: TW and SD rats demonstrated the highest levels of anxiety- and depression-like behaviors, while EX-TW rats did not exhibit anxiety- and depression-like behaviors. TW and SD rats showed no impairments in STM. However, TW and SD rats showed impairments in LTM, and exercise rescued LTM impairments in EX-TW rats. CONCLUSIONS: This study demonstrates that rats subjected to direct experience or witness of social defeat exhibited PTSD-like behaviors, while moderate treadmill exercise prevented trauma witness-induced behavioral impairments. These studies have important translational value suggesting that prior treadmill exercise might provide resilience to stressful stimuli and perhaps mitigate the witnessing effects of traumatic events.