Post-Traumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder that arises following exposure to an extreme stress. PTSD is characterized by five primary trauma-related symptom clusters, including symptoms of negative mood and hyperresponsivity to the traumatic event. Regrettably, the current therapy options are not highly effective. Therefore, prevention of PTSD is crucial and potentially applicable. Prazosin is an anti-adrenergic medication that is used to reduce nightmares in patient with PTSD, and can also mitigate the noradrenergic dysfunction caused by trauma. Here we show that administration of prazosin prior to the trauma prevented learned helplessness behavior in adult male rats. We show that the animals that were exposed to three days of inescapable foot shocks preceded by prazosin injections have fewer prazosin-treated animals showing learned helplessness compared to saline-treated animals. Nevertheless, there was no significant difference in anxiety-related behavior as measured in the elevated plus maze. Furthermore, the results of in vivo electrophysiological recordings of the ventral tegmental area shows that the prazosin group has a trend of increased number of active dopaminergic cells per track; this is significant when limited to central region of the ventral tegmental area. Our results demonstrate that prazosin has a potential for prevention of PTSD.