Involvement of monoaminergic and nitrergic pathways in the behavioral effects and acute toxicity of Gomphrena perennis L. tincture in mice

Gomphrena perennis L. possesses a rich phenolic profile and has demonstrated cardiovascular and anti-inflammatory activities; however, its neuropharmacological properties re-main unexplored. The behavioral effects, underlying mechanisms, and acute toxicity of Gomphrena perennis tincture (GphT) were investigated in mice. GphT showed no signs of acute toxicity. Furthermore, it did not alter the number of cross lines in the open field test (OFT), but it induced anxiogenic responses in the elevated plus-maze test (EPM) and the novelty-suppressed feeding test (NSFT), which were reversed by L-NAME, a non-selective nitric oxide synthases inhibitor. GphT also reduced immobility time in the forced swimming test (FST) and the tail suspension test (TST). This antidepressant-like effect was prevented by haloperidol (D1/D2 antagonist), ketanserin (5-HT2A/2C antagonist), L-NAME, and sildenafil (PDE5 inhibitor), while propranolol ({beta}-blocker), prazosin (1-an-tagonist), yohimbine (2-antagonist), and ondansetron (5-HT3-antagonist) did not modify it. Therefore, GphT produced anxiogenic and antidepressant-like effects without im-pairing locomotion. These effects involve dopaminergic and serotonergic pathways and depend on nitric oxide-mediated signaling, suggesting that GphT exerts a modulatory influence on interconnected neurochemical systems.