Abstract

The effects of chronic administration of desimipramine (DMI, 10 mg/kg i.p. daily for 4 or 5 weeks), short-term administration of lithium (Li, 0.2% in food for 10 days) and a combination of these treatments on serotonergic receptors and second messengers were studied in the rat brain. DMI alone had no effect on [3H]5-HT binding but reduced [3H]ketanserin binding in cortical membranes, 5-HT-stimulated inositol phosphate (IP) formation in cortical slices and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes. Li alone reduced [3H]5-HT binding and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes, and also reduced [3H]ketanserin binding and 5-HT-stimulated IP formation in the cortex. The two treatments combined in general produced effects similar to those of Li alone, but the decrease in [3H]ketanserin binding in cortical membranes was significantly greater than that given by Li alone, whereas the reduction in the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes was significantly greater than that produced by DMI alone. It is concluded 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 serotonergic system in the brain.