Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/physbeh Tempol prevents post-traumatic stress disorder induced memory impairment Karem H. Alzoubi ⁎ , Abeer M. Rababa'h, Omar N. Al Yacoub Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan ARTICLE INFO Keywords: Tempol PTSD Memory Hippocampus Maze ABSTRACT Post-traumatic stress disorder (PTSD) is a mental health disorder that can develop after a terrifying or life threatening event. Multiple symptoms are noticed in patients with PTSD including cognitive impairment, which was shown to be is associated with oxidative stress. Tempol is a highly efficient membrane-permeable anti- oxidant. In this study, we investigated the possible protective effect of tempol on PTSD-induced memory im- pairment. To test this hypothesis, we used single prolonged stress (SPS) model (2 h restrain, 20 min forced swimming, 15 min rest, and 1–2 min diethyl ether exposure) as a model of PTSD. Rats were randomly assigned into four groups: control (provided distilled water), tempol (provided tempol; 80 mg/kg/day by oral gavage for 4 weeks), SPS (exposed to prolonged stress and administered distilled water) and tempol/SPS (exposed to prolonged stress and administered tempol for 4 weeks). We used radial arm water maze to test spatial learning and memory functions and enzyme-linked immunosorbant assay (ELISA) to measure levels of oxidative stress biomarkers in the hippocampus. Results showed that SPS model of PTSD impaired both short and long-term memories (P < 0.05), and chronic tempol administration prevented such effect. Tempol also prevented de- creases in hippocampal catalase, and SOD activities, GSH/GSSG ratio and increases TBARS levels, which were all impaired by SPS model of PTSD (P < 0.05). In conclusion, we suggest a protective effect of tempol adminis- tration against SPS model of PTSD–induced short– and long- term memory impairment, and we believe that this protective effect of tempol is accomplished, at least partly, through prevention of alternation in oxidative stress in the hippocampus. 1. Introduction Post-traumatic stress disorder (PTSD) is a disabling trauma and stressor anxiety psychiatric disorder that is developed after experien- cing or witnessing traumatic events such as natural disasters, war dis- asters, violent attacks or sexual assault [24,48]. Cognitive symptoms of PTSD include intrusive memories, avoidance of thoughts, feelings, or reminders of the trauma, and inability to recall parts of the trauma [31]. Deterioration of cognitive function was also seen in PTSD patients [33]. Several reports have shown verbal declarative memory deficits during PTSD, among adult patients with PTSD who have been through combat [45], childhood abuse [10], rape [26], and political violence [27]. On the other hand, studies on PTSD animal models reported structural changes in hippocampus in relation to PTSD [21,35–37,47]. Additionally, PTSD animal models have shown hippocampus memory deficits that was evaluated by different tasks, such as eight-arm radial maze [35], Morris water maze [44,55,56], and radial arm water maze [15,42]. The exact mechanism by which PTSD-induced memory impairment is not clearly understood. Using PTSD animal models, several studies linked the clinical manifestations of PTSD to the increased oxidative stress and the suppressed antioxidant mechanisms in the brain [18,20,60,63]. Thus, PTSD potentiates oxidative stress that accelerates cellular aging [39]. Using predator animal model of PTSD, a progressive increase in oxidative stress was shown in a time-dependent pattern during the development of PTSD [60]. It was also reported that PTSD patients possess lower antioxidant system activity (GPx, SOD) and higher lipid peroxidation level compared to healthy control subjects [8,9], and therefore, oxidative stress is a possible casual factor for the clinical symptoms of PTSD. Among PTSD patients, a statistically reli- able correlations has been reported between the incidence and symp- tomatic severity of PTSD and oxidative stress biomarkers [54]. PTSD animal models also showed increased reactive oxygen species in hip- pocampus tissues [60]. Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl) is a potent antioxidant that belongs to the nitroxide compounds family https://doi.org/10.1016/j.physbeh.2017.12.002 Received 30 June 2017; Received in revised form 14 October 2017; Accepted 2 December 2017 ⁎ Corresponding author at: Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan. E-mail address: khalzoubi@just.edu.jo (K.H. Alzoubi). Physiology & Behavior 184 (2018) 189–195 Available online 05 December 2017 0031-9384/ © 2017 Elsevier Inc. All rights reserved. T