Differential effect of lithium on 5-HT1 receptor-linked system in regions of rat brain

The effect of chronic administration (0.4% for 30 days) of lithium carbonat e (Li2CO3) on 5-HT1 receptor-linked second messenger system was studied in regions of rat brain. We observed that chronic treatment of Li2CO3, signifi cantly decreased the density of [H-3]5-HT binding sites in cortex (62%), hi ppocampus (64%) and striatum (65%), compared to the control levels. The aff inity of [H-3]5-HT to 5-HT1 binding sites was significantly decreased in al l the regions. A significant decrease in the density of high affinity 5-HT1 A receptor sites was observed in cortex (81%) and hippocampus (42%), withou t change in the affinity of [H-3]8-OH-DPAT for 5-HT1A sites in these region s. 5-HT-stimulated, but not basal adenylyl cyclase activity was significant ly increased in all the regions after Li treatment. The present study concl udes that the increase in the 5-HT-stimulated adenylyl cyclase activity mig ht be attributed to the functional downregulation of 5-HT1 receptors, as th ese are negatively coupled to adenylyl cyclase, suggesting the involvement of 5-HT1 receptor mediated response in the therapeutic efficacy of lithium. (C) 1999 Elsevier Science Ltd. All rights reserved.