Regulation of 5‐HT receptors by corticosteroids: where do we stand?

Chaouloff F(1).

Author information:
(1)Génétique du Stress, CJF 94-05 Inserm-Inra, Université Bordeaux II, France.

Twenty five years ago, experimental procedures such as adrenalectomy and
corticosteroid administration (to intact rats) allowed the recognition of direct
and indirect controls of central 5-HT synthesis rate by corticosteroids. These
effects indicated that the activity of the hypothalamo-pituitary-adrenal (HPA)
axis, whether under basal conditions or during stress, is endowed with a
modulatory action upon serotonergic neurons. Nowadays, in situ hybridisation, in
vitro autoradiography, and radioligand binding on the one hand, and
electrophysiological, behavioural, and neuroendocrinological responses on the
other hand, are tools that allow the analysis of direct corticosteroid effects
upon 5-HT receptors. Among the dozen of 5-HT receptors identified so far, four
receptors (namely the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptors)–and the 5-HT
uptake system–have been the focus of studies aimed at detecting corticosteroid
modulatory effects. The results that are reviewed herein indicate that
hippocampal 5-HT1A receptors are under the tonic inhibitory control of
corticosterone. This control is directly exerted at the level of the 5-HT1A
receptor gene, essentially through mineralocorticoid receptors; as well,
electrophysiological findings bring support for an additional modulation of
hippocampal 5-HT1A receptor-mediated functions by indirect (ie 5-HT1A receptor
gene-independent) genomic actions of corticosteroids. In keeping with the
respective effects of stressful stimuli and psychotropic drugs upon the HPA axis
and central serotonergic systems, it is likely that these corticosteroid-5-HT1A
receptor interactions in the hippocampus have consequences in the pathophysiology
of mood disorders. However, because the data regarding a corticosteroid control
of other 5-HT receptors are either scarce and contradictory (eg 5-HT1B, 5-HT2A,
5-HT2C receptors and 5-HT uptake systems) or lacking, it is at the present time
unknown whether corticosteroids exert other effects on 5-HT receptor-mediated
functions, including those related to homeostasis.

DOI: 10.1111/j.1472-8206.1995.tb00289.x
PMID: 7557817 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus