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.
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