Tempol Treatment Reduces Anxiety-Like Behaviors Induced by Multiple Anxiogenic Drugs in Rats

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.

Grape powder treatment prevents anxiety-like behavior in a rat model of aging

“…This is in agreement with our previous studies in which we had reported antianxiety effect of GP in 3 separate rodent models [18,27,36]. Anxiety-like behaviors induced by L-buthionine-(S,R)-sulfoximine [18], single prolonged stress [27], and ovariectomization [28] were prevented with GP treatment.…”

“…This is in tandem with our previous observations in which behavioral and cognitive impairments noted in other rodent models [3,27,28] were associated with elevated plasma corticosterone levels [3,27,28]. In addition to examining the protective role of GP using systemic evaluation of stress, we also examined the level of neuronal stress using a biochemical marker of neuronal activation, c-fos [34,36]. We focused on 3 regions of the brain, namely, the hippocampus, amygdala, and prefrontal cortex, areas implicated in anxiety, cognition, and Fig.…”

“…Our laboratory in 3 separate studies has reported that CTGC freeze-dried GP prevented pharmacologically and psychologically induced anxiety and depression-like behaviors and also improved learning and memory function in rats [18,27,36]. In the present study, protective effect of grapes on age-related anxiety and memory deficits were examined using the F344 rat model of aging.…”

“…Interestingly, these same brain areas also are considered to be highly susceptible to oxidative stress [27,29,36]. This is particularly relevant considering the protective effects of GP on aging-induced behavioral and cognitive deficits and the fact that the protective effects are most likely attributable to the antioxidant-rich nature of GP [38].…”

Injection of Cocaine-Amphetamine Regulated Transcript (CART) peptide into the nucleus accumbens does not inhibit caffeine-induced locomotor activity: Implications for CART peptide mechanism

“…Caffeine alters LMA at low doses (10-30 mg/kg), and at higher doses (≥ 50 mg/kg), it exerts anxiogenic effects (Baldwin and File, 1989, Bhattacharya et al , 1997, Collins et al , 2010, Cook and Beardsley, 2003, El Yacoubi et al , 2000, Garrett and Holtzman, 1994, Halldner et al , 2004, Kaplan et al , 1992, Kuzmin et al , 2006, Patki et al , 2015, Solinas et al , 2002, Svenningsson et al , 1995, Zhang et al , 2011). Higher doses of caffeine alter CART peptide levels in the NAc (Cho et al , 2015).…”