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 (40mg/kg, per oral, p.o.) in the FST was blocked with yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), alpha-methyl-para-tyrosine methyl ester (AMPT, 100mg/kg, i.p., an inhibitor of tyrosine hydroxylase), efaroxan (1mg/kg, i.p., an imidazoline I(1)/alpha(2)-adrenoceptor antagonist), idazoxan (0.06mg/kg, i.p., an imidazoline I(2)/alpha(2)-adrenoceptor antagonist), antazoline (5mg/kg, i.p., a ligand with high affinity for the I(2) receptor), haloperidol (0.2mg/kg, i.p., a non selective dopamine receptor antagonist), SCH23390 (0.05mg/kg, subcutaneously, s.c., a dopamine D(1) receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D(2) and D(3) receptor antagonist) but was not reversed by prazosin (1mg/kg, intraperitoneally, i.p., an alpha(1)-adrenoceptor antagonist) and caffeine (3mg/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. Copyright 2010 Elsevier Inc. All rights reserved.