Functional effects of corticosterone on 5-HT1A and 5-HT1B receptor activity in rat brain: in vivo microdialysis studies

Abstract

Glucocorticoid hormones are known to be elevated in depression, and to interact with serotonin 5-HT1A 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-HT1A and also 5-HT1B 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-HT1A receptor activity, as measured by the effect of a challenge dose (0.2 mg/kg s.c.) of the 5-HT1A 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-HT1B receptor activity, as measured by the effect of the 5-HT1B 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-HT1A 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-HT1B receptor activity after chronic administration of antidepressant drugs complements the increases in 5-HT1B receptor number observed in animal models of depression.