EFFECTS OF PRETREATMENT WITH CLONIDINE, LITHIUM AND QUININE ON THE ACTIVITIES OF ANTIDEPRESSANT DRUGS IN THE MOUSE TAIL SUSPENSION TEST

The aim of the present study was the investigation of pretreatment eff ects 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 ac ting on noradrenergic and/or serotonergic systems in the mouse tail su spension test. Drugs used in the present study included: the tricyclic antidepressants imipramine and dothiepin, the heterocyclic antidepres sant trazodone, the 5-HT reuptake inhibitor (SSRI) fluoxetine, the aty pical antidepressants mianserin and iprindole, the 5-HT1A receptor ago nist ipsapirone, the 5-HT2A/2C receptor antagonist ritanserin, and the 5-HT3 receptor antagonist ondansetron. Clonidine, lithium and quinine differentially enhanced the effects of several psychotropic drugs adm inistered at sub-active doses. The activity of iprindole (32 mg/kg, ip ) was not potentiated by pretreatment with clonidine, lithium or quini ne. Our results suggest that lithium exerted additive effects via post synaptic 5-HT1A receptor activation, quinine via potassium ion channel blockade of 5-HT3 receptors, while clonidine did so primarily via act ion at 5-HT2 receptors.