evaluation of anti-anxiety effects of nanomicelles silimarin and citicolin co-treatment on anxiolytic behaviors and bdnf expression in a mice model of restraint stress

Aim and background: this study evaluated the effects of citicoline and silymarin nanomicelles (smnm) in repeated restraint stress (rrs). methods: mice were exposed to rrs for three consecutive days, 3 hrs. each day. on day four of the study, intraperitoneal injections (i.p.) of smnm (25 and 50 mg/kg) and citicoline (25 and 75 mg/kg), and a combination of smnm and citicoline at dose of 25 mg/kg were initiated. on day eighteen, anxiety-like behavior, behavioral despair and exploratory behavior were evaluated using the elevated plus maze (epm)and the open field test (oft), respectively. after that, the prefrontal cortex and the hippocampus were dissected measuring brain-derived neurotrophic factor (bdnf) and tumor necrosis factor-alpha (tnf-α) through western blot and elisa, respectively. results and discussion: anxiety-like behavior in the emp was enhanced in mice exposed to rrs by reductions in open arm time (oat%) and open arm entry (oae%). in the oft, general motor activity raised. further, they lost body weight, reduced tissue bdnf expression while increased tnf-α. conversely, post-treatments of smnm and citicoline could reduce anxiety-like behaviors. moreover, they restored general locomotor activity and body weights. besides, they increased bdnf expression while reduced tnf-α. notably, the protective effects were enhanced when a combination of smnm and citicoline were treated.conclusion: combination of smnm and citicoline synergistically improved cognitive and biochemical impairments in rrs mice alleviating the inflammation, while upregulating the hippocampal bdnf.