We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. mind (4.3mmol/day time) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later on all organizations were subjected to behavioral assessments. Anxiety-like behavior checks (open-field light-dark and elevated plus maze) suggested that tempol prevented anxiogenic drug-induced anxiety-like behavior in rats. Furthermore anxiogenic drug-induced increase in stress examined via plasma corticosterone and increased oxidative stress levels assessed via plasma 8-isoprostane were prevented with tempol CiMigenol 3-beta-D-xylopyranoside treatment. Protein carbonylation assay also suggested preventive effect of tempol in the prefrontal cortex brain region of rats. Antioxidant protein expression and pro-inflammatory cytokine levels indicate compromised CiMigenol 3-beta-D-xylopyranoside antioxidant defense as well as an imbalance of inflammatory response. Introduction Clinical evidence suggests that oxidative metabolism affects regulation of stress. Several groups have proposed a link between oxidative stress and certain stress disorders including obsessive-compulsive disorder and panic disorder [1 2 Most clinical studies suggest associative links between oxidative stress and anxiety but causal role of oxidative stress in stress is not known. Animal studies on the other hand have been more useful in clarifying role of oxidative stress in anxiety-like behaviors. Several laboratories including ours have reported that pharmacological induction of oxidative stress causes anxiety-like behaviors in rats and prevention of oxidative stress with antioxidant tempol treatment mitigates anxiety-like behaviors [3-5]. These interesting studies prompted us Rabbit Polyclonal to OR51B2. to examine whether behavioral outcome of pharmacological induction of oxidative stress can be mimicked in situations where oxidative stress occurs as a consequence of psychological stress. Results from individual studies have revealed that the psychological stress induced via interpersonal stress  single-prolonged stress  estrogen depletion  and sleep deprivation  induce oxidative stress and also cause anxiety-like behaviors in rats. In one model of psychological stress antioxidant treatment completely rescued anxious phenotype of ovariectomized female rats [8 10 CiMigenol 3-beta-D-xylopyranoside These studies have led us to test the following postulation-and in vivo. It is a membrane-permeable radical scavenger a pro-survival agent  safe to use in animals  and also crosses blood brain barrier . In addition to measuring the effect of antioxidant treatment on caffeine/FG-7142-induced anxiety-like behaviors in rats we also examined the status of oxidative stress both systemically as well as within three crucial brain areas considered vital for stress namely hippocampus amygdala CiMigenol 3-beta-D-xylopyranoside and the prefrontal cortex . Levels of corticosterone (systemic marker of psychological stress) also were examined. Protein expression levels of c-fos (a biochemical marker of stress) the enzymes of antioxidant defense including glyoxalase (GLO)-1 glutathione reductase (GSR)-1 manganese (Mn) superoxide dismutase (SOD) and copper-zinc (Cu/Zn) SOD inflammatory markers and a regulator of G-protein signaling protein (RGS)-2 also were examined. Methods and Materials Animals Male Sprague Dawley rats (250-275 g) obtained from Charles River Wilmington MA were housed in a climate-controlled room on a 12-h light/dark cycle (lights on at 0700 h). Rats were provided with food and water ad libitum. Ethics Statement All experiments were conducted in accordance with the NIH guidelines using protocols approved from the University of Houston Animal Care and Use Committee. Osmotic pump implantation One day before implantation osmotic pumps were primed as follows: the pumps were filled with tempol (dissolved in saline; 4.3mmol/day) or saline attached by catheter tubing to an L-shaped cannula and left overnight in isotonic saline answer at 37°C. The rats were anesthetized with i.p. injections of a mixture of ketamine (100 mg/kg; Ketaset Fort Dodge animal health IA) xylazine (2.5 mg/kg; Xyla-Jet Phoenix Pharmaceuticals Inc MO)..