Modulation of the serotonin S2-receptor in brain after chronic lithium.

In vivo effects of chronic lithium administration on dopaminergic and serotonergic receptor binding were studied in the striatum and cerebral cortex of the rat. [3H]Domperidone was used as the ligand for the dopaminergic receptor, and [3H]ketanserin for the serotonergic system. Long-term ingestion of lithium (2-3 months) resulted in high levels of lithium in the cerebral cortex and significantly higher potassium levels; the sodium content remained at normal levels. The kinetic constants (Kd and Bmax) of [3H]domperidone binding sites measured in the striatum did not show any deviation from control values, but the receptor concentration (Bmax) of [3H]ketanserin binding sites was significantly reduced in the cerebral cortex of lithium-treated rats. The apparent dissociation constant (Kd) was not changed. The results indicate that the serotonergic component of the [3H]spiperone binding site, which we had previously found to be affected by chronic lithium treatment and which was shown by Peroutka and Snyder to be the 5-HT2 receptor, is selectively affected by lithium.