The immunomodulatory tellurium compound ammonium trichloro (dioxoethylene-O,O′) tellurate reduces anxiety-like behavior and corticosterone levels of submissive mice

Moshe Gross, Emanuel Stanciu, Dvora Kenigsbuch-Sredni, Benjamin Sredni, Albert Pinhasov
2017 Behavioural Pharmacology  
Ammonium trichloro (dioxoethylene-O,O′) tellurate (AS101) is a synthetic organotellurium compound with potent immunomodulatory and neuroprotective properties shown to inhibit the function of integrin αvβ3, a presynaptic cellsurface-adhesion receptor. As partial deletion of αvβ3 downregulated reuptake of serotonin by the serotonin transporter, we hypothesized that AS101 may influence pathways regulating anxiety. AS101 was tested in the modulation of anxiety-like behavior using the selectively
more » ... the selectively bred Submissive (Sub) mouse strain that develop anxietylike behavior in response to an i.p. injection. Mice were treated daily with AS101 (i.p., 125 or 200 μg/kg) or vehicle for 3 weeks, after which their anxiety-like behavior was measured in the elevated plus maze. Animals were then culled for the measurement of serum corticosterone levels by ELISA and hippocampal expression of brain-derived neurotrophic factor (BDNF) by RT-PCR. Chronic administration of AS101 significantly reduced anxiety-like behavior of Sub mice in the elevated plus maze, according to both time spent and entries to open arms, relative to vehicle-treated controls. AS101 also markedly reduced serum corticosterone levels of the treated mice and increased their hippocampal BDNF expression. Anxiolyticlike effects of AS101 may be attributed to the modulation of the regulatory influence integrin of αvβ3 upon the serotonin transporter, suggesting a multifaceted mechanism by which AS101 buffers the hypothalamic-pituitary-adrenal axis response to injection stress, enabling recovery of hippocampal BDNF expression and anxiety-like behavior in Sub mice. Further studies should advance the potential of AS101 in the context of anxiety-related disorders. Behavioural Pharmacology 00:000-000
doi:10.1097/fbp.0000000000000319 pmid:28590303 fatcat:aeup2efwavagndbwjsivruy4ji