Evidence for the involvement of the noradrenergic system, dopaminergic and imidazoline receptors in the antidepressant-like effect of tramadol in mice

The involvement of the noradrenergic system, imidazoline, dopaminergic and adenosinergic receptors in the antidepressant-like action of tramadol in the mouse forced swimming test (FST) was evaluated in this study. The antidepressant-like effect of tramadol (40 mg/kg, per oral, p.o.) in the FST was blocked with yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), alpha-methyl-para-tyrosine methyl ester (AMPT, 100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), efaroxan (1 mg/kg, i.p., an imidazoline I-1/alpha(2)-adrenoceptor antagonist), idazoxan (0.06 mg/kg, i.p., an imidazoline I-2/alpha(2)-adrenoceptor antagonist), antazoline (5 mg/kg, i.p., a ligand with high affinity for the 12 receptor), haloperidol (0.2 mg/kg, i.p., a non selective dopamine receptor antagonist), SCH23390 (0.05 mg/kg, subcutaneously, s.c., a dopamine D-1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D-2 and D-3 receptor antagonist) but was not reversed by prazosin (1 mg/kg, intraperitoneally, i.p., an alpha(1)-adrenoceptor antagonist) and caffeine (3 mg/kg, i.p., a nonselective adenosine receptor antagonist). Monoamine oxidase-A and -B (MAO-A and MAO-B) activities were neither inhibited in the whole brain nor in specific brain regions of mice treated with tramadol. These data demonstrated that the antidepressant-like effect caused by oral administration of tramadol in the mouse FST is mediated by the noradrenergic system, dopaminergic and imidazoline receptors. (C) 2010 Elsevier Inc. All rights reserved.