Pharmacological modulation of anxiety‑like and depression‑like behaviors in nerve‑ligated mice: regarding the effects of citicoline and bupropion

Neuropathic pain is a condition that results from nerve injury. There is a relationship between neuropathic pain and mood disorders. Citicoline, when used as a dietary supplement, exhibits neuroprotective, antidepressant, and anxiolytic properties. Moreover, bupropion is an atypical antidepressant with unique pharmacologic properties. We sought to investigate the effects of citicoline and bupropion as well as their possible interaction on the control of anxiety‑ and depression‑like behaviors in nerve‑ligated mice. Unilateral sciatic nerve ligation was performed on the right hind limb. Anxiety‑ and depression‑like behaviors were measured using the elevated plus‑maze and the tail suspension test, respectively. The results showed that sciatic nerve ligation decreased the percentage of time spent in the open arms of the elevated plus‑maze and increased the immobility time in the tail suspension test, displaying anxiogenic‑ and depressant‑like responses in the nerve‑ligated mice. Intraperitoneal administration of citicoline increased the percentage of time spent in the open arms and diminished the immobility time of the tail suspension test compared to the saline group, showing anxiolytic and antidepressant‑like responses. Additionally, the injection of bupropion induced antianxiety‑ and antidepressant‑like responses increasing the percentage of time spent in the open arms and reducing immobility time in nerve‑ligated mice. Co‑injection of bupropion and citicoline potentiated the antidepressant property of bupropion in nerve‑ligated mice. Additionally, we determined an additive effect between bupropion and citicoline on the generation of anxiolytic and antidepressant‑like behaviors in the nerve‑ligated mice. Based on these results, we concluded that there is a crosstalk between bupropion and citicoline in the control of anxiety‑ and depression‑like behaviors in the nerve‑ligated mice.