Interaction of lithium with 5-HT1B receptors in depressed unipolar patients treated with clomipramine and lithium versus clomipramine and placebo:: preliminary results

Lithium is commonly used in combination with antidepressant drugs as a treatment for refractory depression; less often, it is used in non-resistant depression. The aim of this study was to examine the interaction of lithium with 5-HT1B receptors in 10 non-resistant unipolar depressed patients treated with clomipramine + lithium (C+L) vs. clomipramine + placebo (C + P). A mediation of the serotonergic system has been proposed in the literature to explain the clinical effect of lithium. Indeed, in a previous study of healthy human blood platelets, we demonstrated the interaction of lithium with adenylate, cyclase activity coupled to 5-HT1B receptors. The functional activity of these receptors was measured by studying the inhibitory effect of L694,247, a 5-HT1B receptor agonist, on the adenylate cyclase activity determined by the production of cAMP. Using the same technique in the present study, we found that lithium significantly reduced the inhibition of adenylate cyclase activity induced by 5-HT1B receptor activation. This result confirms the specific interaction of lithium with 5-HT1B receptors. Moreover, a correlation between the percentage of 5-HT1B receptor-dependent adenylate cyclase inhibition and the clinical benefit of lithium was established, suggesting 5-HT1B receptors may be a target for the therapeutic effect of lithium (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.