Prolonged corticosterone treatment alters the responsiveness of 5-HT 1A receptors to 8-OH-DPAT in rat CA1 hippocampal neurons

Abstract

Hippocampal 5-HT(1A) receptors have been shown to be suppressed by glucocorticoids in a variety of animal studies, however the molecular mechanism and the functional meaning of this effect are still not well understood. The present study was designed to investigate the impact of repeated administration of corticosterone (10 mg/kg s.c. twice daily for 7 days) on the functional consequences of 5-HT(1A) receptor stimulation measured electrophysiologically in hippocampal slices. Additionally, the effects of corticosterone on 5-HT(1A) receptor binding and on receptor mRNA levels in the hippocampus were studied. Prolonged, but not acute treatment with corticosterone attenuated (+/-)-8-hydroxy-2-di- N-propylamino)tetralin hydrobromide (8-OH-DPAT)-induced inhibition of population spikes, and 8-OH-DPAT-induced hyperpolarization in rat CA1 hippocampal neurons. Chronic, but not acute treatment with corticosterone also decreased 5-HT(1A) receptor binding in the CA1 region (in the ventral part only) and the dentate gyrus. A single dose of corticosterone increased [(3)H]8-OHDPAT binding in the dentate gyrus and in the CA3 and CA4 hippocampal regions. Only acute, but not prolonged treatment with corticosterone decreased the level of 5-HT(1A) receptor mRNA in the CA1 region and dentate gyrus of the hippocampus. 5-HT turnover in the hippocampus was not influenced by chronic corticosterone. It is concluded that a chronically elevated level of corticosterone can induce functional desensitization of 5-HT(1A) receptors in the CA1 area of the hippocampus, although this effect is not always followed consequently by decreases in 5-HT(1A) receptor synthesis in this or other areas of the hippocampus.

Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine

“…Paroxetine, by inhibiting serotonin reuptake, would be expected to enhance serotonin availability to these serotonergic receptors. This contrasts with corticosteroids which have been reported to reduce 5-HT 1A receptor mRNA expression [15] or the response of 5-HT 1A receptors in the hippocampus [16] . Previous research has found that the effect of corticosteroids on cell proliferation is dependent on N-methyl-D-aspartate (NMDA) receptors, since inhibition of NMDA receptors prevented the corticosteroid-mediated inhibition of cell proliferation [17] .…”

Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

“…In consistent with these previous reports, diabetic mice showed the increases in plasma corticosterone levels in our present result. Longterm corticosterone treatment induced dysfunction of 5-HT 1A receptors to 8-OH-DPAT in behavioral and electrophysiological studies (Haleem, 1992;Czyrak et al, 2002). Therefore, it is possible that the dysfunction of 5-HT 1A receptors may be due to the chronic high corticosterone levels in diabetic mice.…”

The 5-HT1A Receptor Full Agonist, 8-OH-DPAT Inhibits ACTH-Induced 5-HT2A Receptor Hyperfunction in Rats: Involvement of 5-HT1A Receptors in the DOI-Induced Wet-Dog Shakes in ACTH-Treated Rats

“…It was reported that chronic treatment with corticosterone decreased 5-HT 1A receptor binding and the levels of 5-HT 1A receptor mRNA in the hippocampus. 7,8) We demonstrated that hypercorticism, which raises circulating corticosterone levels, decreased the 5-HT 1A receptor binding in hippocampal membranes. 9) Thus, the enhancement of the hypothalamic-pituitary-adrenal axis produced dysfunction of the 5-HT 1A receptor mechanism.…”

“…7) Additionally, chronic but not acute treatment with corticosterone decreased 5-HT 1A receptor binding in rat CA1 hippocampus region (in the ventral part only) and the dentate gyrus. 8) Regarding 5-HT 1A receptor binding, the general consensus is that the chronically elevated corticosterone down-regulates 5-HT 1A receptor binding in the hippocampus. In the present study, the inhibitory effect of 8-OH-DPAT on the DOI-induced wet-dog shake response was not inhibited by the chronic administration of ACTH.…”