Abstract
We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. Using animal models, we also have established that psychological stress induces OS and leads to anxiety-like behaviors. All evidence points towards the causal role of OS in anxiety-like behaviors. To fully ascertain the role of OS in anxiety-like behaviors, it is reasonable to test whether the pro-anxiety effects of anxiogenic drugs caffeine or N-methyl-beta-carboline-3-carboxamide (FG-7142) can be mitigated using agents that minimize OS. In this study, osmotic pumps were either filled with antioxidant tempol or saline. The pumps were attached to the catheter leading to the brain cannula and inserted into the subcutaneous pocket in the back pocket of the rat. Continuous i.c.v. infusion of saline or tempol in the lateral ventricle of the brain (4.3mmol/day) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later all groups were subjected to behavioral assessments. Anxiety-like behavior tests (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 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 antioxidant defense as well as an imbalance of inflammatory response.
Highlights
Clinical evidence suggests that oxidative metabolism affects regulation of anxiety
These interesting studies prompted us 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
Number of fecal boli was significantly higher in anxiogenic drug injected rats when compared to controls or T+CAFFEINE/FG-7142 (SALINE: 2.33 ± 0.6, T: 1.6 ± 0.3, CAFFEINE: 7.4 ± 1.1, FG-7142: 7.4 ± 1.2, T+CAFFEINE: 3.1 ± 0.5, T+FG-7142: 3.5 ± 1.2, F(5,33) = 4.79, p
Summary
Clinical evidence suggests that oxidative metabolism affects regulation of anxiety. Several groups have proposed a link between oxidative stress and certain anxiety disorders including obsessivecompulsive disorder and panic disorder [1,2]. Animal studies on the other hand have been more informative 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 [3,4,5]. These interesting studies prompted us 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. In one model of psychological stress antioxidant treatment completely rescued anxious phenotype of ovariectomized female rats [8,10]
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