Modulatory effect of diphenyl diselenide in Carioca High- and Low-conditioned Freezing rats.

Diphenyl diselenide ([PhSe]2)is an organoselenium compound that has interesting pharmacological properties, including antioxidant, glutathione peroxidase-mimetic, and neuroprotective effects. The objective of the present study was to investigate the possible modulatory effect of (PhSe)2 in 17th-generation Carioca high-and low-conditioned freezing (CHF and CLF) rats, an animal model of generalized anxiety disorders. (PhSe)2 was administered at three doses (10, 50, and 100mg/kg) in CHF and CLF rats, and their anxiety-like profiles (conditioned freezing patterns) were measured before and 30min after treatment. A significant difference was found in freezing scores between CHF and CLF animals before treatment (t70=12.50, p<0.001). Treatment with (PhSe)2 at 10 and 50mg/kg decreased freezing in CHF rats but significantly increased freezing at 100mg/kg. (PhSe)2 increased freezing in CLF animals at 50 and 100mg/kg (p<0.01). These results indicate that (PhSe)2 exerts both anxiolytic- and anxiogenic-like effects in bi-directional rat lines. Distinct genetic profiles of the CHF and CLF lines may influence biochemical functions and lead to differential responses to aversive situations and various drugs like (PhSe)2.

Association of oxidative stress to the genesis of anxiety: implications for possible therapeutic interventions.

Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders.