Functional effects of corticosterone on 5-HT(1A) and 5-HT(1B) receptor activity in rat brain: in vivo microdialysis studies.
Glucocorticoid hormones are known to be elevated in depression, and to interact with serotonin 5-HT(1A) receptors at both the presynaptic and postsynaptic levels. Since one of the presumed mechanisms of action of antidepressant drugs is induction of changes in sensitivity of 5-HT(1A) and also 5-HT(1B) receptors, the effects of repeated administration of corticosterone (50 mg/kg s.c. b.i.d. for 10 days) on activities of these receptors were determined using in vivo microdialysis in freely moving rats. Presynaptic 5-HT(1A) receptor activity, as measured by the effect of a challenge dose (0.2 mg/kg s.c.) of the 5-HT(1A) agonist 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) to reduce 5-HT levels in the hypothalamus, was not affected by corticosterone administration. Presynaptic 5-HT(1B) receptor activity, as measured by the effect of the 5-HT(1B) receptor antagonist (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide (GR 127935) (5 mg/kg s.c.) to increase 5-HT levels, was increased in hypothalamus but not hippocampus of corticosterone-treated rats. Postsynaptic 5-HT(1A) receptor activity, as measured by the effect of 8-OH-DPAT to increase cyclic AMP levels in the hippocampus, was not affected by corticosterone administration. The decrease in presynaptic 5-HT(1B) receptor activity after chronic administration of antidepressant drugs complements the increases in 5-HT(1B) receptor number observed in animal models of depression.
Gur
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E
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, PO Box 12000, 91120, Jerusalem, Israel.
Dremencov
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E
Lerer
B
B
Newman
M E
ME
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005576:Colforsin; C090701:GR 127935; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP; D003345:Corticosterone