Inhibitory effect of lithium on neuroleptic and serotonin receptors in rat brain.

We investigated the effect of acute and chronic administration of lithium on neuroleptic receptors ([3H]spiroperidol binding sites) and serotonin receptors ([3H]serotonin binding sites) in rat brain. In the limbic-forebrain, both acute and chronic lithium treatment significantly reduced the density (Bmax) of neuroleptic receptors, without affecting the affinity (Kd) of those receptors. However, lithium treatment had no apparent effect on neuroleptic receptors in the caudate-putamen and frontal cortex in either acute or chronic administrations. On the other hand, acute lithium administration markedly decreased the Kd and Bmax of serotonin receptors in the hippocampus, but not in the cerebral cortex; this distinct observation was also found in animals chronically treated with lithium. These results indicate that lithium has an inhibitory effect on neuroleptic receptors in the limbic-forebrain and on serotonin receptors in the hippocampus. Therefore, it is possible to postulate that these effects of lithium in specific brain regions may be related to the therapeutic mechanism of this drug in affective disorders.