No alterations in the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity in the hippocampal membranes from rats chronically treated with lithium or antidepressants.
In order to determine the relevance of 5-HT1A-related signal transduction in the mode of action of lithium and antidepressants, the effects of long-term treatment with these drugs on the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity were investigated in the rat hippocampal membranes. Chronic administration of antidepressants altered neither the [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT) binding sites nor the inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT. Long-term treatment with lithium did not affect the inhibitory effect of 5-HT on the forskolin-stimulated adenylate cyclase activity, either. Neither the stimulation by forskolin nor the inhibition by guanyl-5'-ylimidodiphosphate (Gpp(NH)p) of adenylate cyclase activity was not influenced by lithium treatment, suggesting that lithium has no effects on the components of adenylate cyclase system distal to the 5-HT1A receptors. These results indicate that the 5-HT1A-mediated neural transmission has not such an important relevance in the mechanisms of action of lithium or antidepressants.
Odagaki
Y
Y
Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Koyama
T
T
Yamashita
I
I
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D006624:Hippocampus / Q000201:enzymology*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D005576:Colforsin; D008094:Lithium; D000262:Adenylyl Cyclases