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 carbonate (Li2CO3) on 5-HT1 receptor-linked second messenger system was studied in regions of rat brain. We observed that chronic treatment of Li2CO3, significantly decreased the density of [3H]5-HT binding sites in cortex (62%), hippocampus (64%) and striatum (65%), compared to the control levels. The affinity of [3H]5-HT to 5-HT1 binding sites was significantly decreased in all the regions. A significant decrease in the density of high affinity 5-HT1A receptor sites was observed in cortex (81%) and hippocampus (42%), without change in the affinity of [3H]8-OH-DPAT for 5-HT1A sites in these regions. 5-HT-stimulated, but not basal, adenylyl cyclase activity was significantly increased in all the regions after Li treatment. The present study concludes that the increase in the 5-HT-stimulated adenylyl cyclase activity might be attributed to the functional downregulation of 5-HT1 receptors, as these are negatively coupled to adenylyl cyclase, suggesting the involvement of 5-HT1 receptor mediated response in the therapeutic efficacy of lithium.
Subhash
M N
MN
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Subhash@nimhans.kar.nic.in
Vinod
K Y
KY
Srinivas
B N
BN
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism
D011985:Receptors, Serotonin; D008094:Lithium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases