[Studies on lithium potentiation of antidepressant treatment]

The effects of chronic administration of clomipramine or citalopram (CMI or CIT, 20 mg/kg i.p. daily for 19 days) with/without short-term administration of lithium (Li, 2 mEq/kg i.p. daily for 5 days) on the concentration of monoamines and their metabolites and serotonergic receptors were studied in the rat cerebral cortex. Li or CMI by itself had no effects on the concentration of monoamines and their metabolites, but a combination of CMI and Li increased that of 5-HIAA. CIT alone increased that of 5-HIAA, and a combination of CIT and Li increased that of 5-HIAA more than CIT alone. There were no changes in 5-HT or 5-HIAA after acute administration of CMI or CIT with/without Li. For the serotonergic receptors, [3H] 8-OH-DPAT and [3H] paroxetine binding did not change in any of the treatments. CMI alone or a combination of CMI and Li reduced [3H] ketanserin binding, but Li did not potentiate this effect. It is speculated that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the activation of presynaptic serotonergic system.