Effects of pretreatment with clonidine, lithium and quinine on the activities of antidepressant drugs in the mouse tail suspension test

Summary— The aim of the present study was the investigation of pretreatment effects with clonidine (0.06 mg/kg, intraperitoneal [ip]), lithium (1 mEq, ip) or quinine (0.5 mg/kg, ip) on the activities of various drugs acting on noradrenergic and/or serotonergic systems in the mouse tail suspension test. Drugs used in the present study included: the tricyclic antidepressants imipramine and dothiepin, the heterocyclic antidepressant trazodone, the 5-HT reuptake inhibitor (SSRI) fluoxetine, the atypical antidepressants mianserin and iprindole, the 5-HT_1A receptor agonist ipsapirone, the 5-HT_2A/2C receptor antagonist ritanserin, and the 5-HT₃ receptor antagonist ondansetron. Clonidine, lithium and quinine differentially enhanced the effects of several psychotropic drugs administered at sub-active doses. The activity of iprindole (32 mg/kg, ip) was not potentiated by pretreatment with clonidine, lithium or quinine. Our results suggest that lithium exerted additive effects via postsynaptic 5-HT_1A receptor activation, quinine via potassium ion channel blockade of 5-HT₃ receptors, while clonidine did so primarily via action at 5-HT₂ receptors.