Effect of thioperamide on modified forced swimming test-induced oxidative stress in mice

This study was designed i) to investigate the role of histamine H-3-receptor ligands on mouse modified forced swimming test, a method that distinguishes the catecholaminergic behaviour with that of serotonergic compounds and ii) to evaluate the role of free radicals in mediation of such effects. Swiss strain albino mice were treated with different doses of histamine H-3-receptor antagonist thioperamide (3.75, 7.5 and 15 mg/kg intraperitoneally) and agonist (R)-alpha-methylhistamine (5 mu g intracerebroventricularly). The climbing, swimming and immobility times were recorded for 6 min. Immediately after modified forced swimming test, the animals were sacrificed and parameters of oxidative stress were assessed in the brain by measuring the thiobarbituric acid reactive substance (TBARS), glutathione (GSH) and catalase levels. Thioperamide (7.5 and 15 mg/kg intraperitoneally) dose-dependently decreased immobility time and increased swimming time but not climbing time. The behaviour of mice treated with (R)-alpha-methylhistamine was similar to that of control mice. A significant reduction in GSH and an increase in catalase levels were observed in brains of mice exposed to modified forced swimming test. Thioperamide pretreatment dose-dependently reversed such an alteration in oxidative stress parameters. (R)-alpha-methylhistamine caused a reversal of altered catalase but not GSH levels. Thioperamide shows antidepressant effects in the modified forced swimming test and causes a reversal of the test-induced oxidative stress indicating its antioxidant potential. The antidepressant effect of thioperamide appears to be mediated via serotonergic and/or antioxidant mechanisms.