Regulation of central corticosteroid receptors following short-term activation of serotonin transmission by 5-hydroxy-L-tryptophan or fluoxetine
by
Semont A, Fache M, Hery F, Faudon M, Youssouf F, Hery M
Laboratoire des Interactions fonctionnelles en Neuroendocrinologie,
INSERM U501, Universite de la Mediterranee,
IFR Jean-Roche, UER de Medecine Nord,
Marseille, France.
J Neuroendocrinol 2000 Aug; 12(8):736-44

ABSTRACT

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis function characterized by a decreased negative feedback capacity are often associated with affective disorders and are corrected by treatment with antidepressant drugs. To gain a better understanding of the effects of the antidepressant drug fluoxetine, a specific serotonin (5-HT) reuptake inhibitor, on central corticosteroid receptors, the effects of short-term activation of serotonin transmission on central corticosteroid receptor expression were analysed in adrenalectomized (ADX) rats either supplemented or not with corticosterone. Serotonin transmission was stimulated either by a single injection of the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP), or by a 2-day treatment with fluoxetine. In ADX rats, administration of 5-HTP decreased hippocampal mineralocorticoid (MR) and glucocorticoid (GR) receptor numbers 24 h later, while their respective mRNAs were unchanged and these effects of 5-HTP were mediated by 5-HT2 receptors. In the hypothalamus, GR mRNAs and binding sites decreased 3 h and 24 h after 5-HTP, respectively. By contrast, fluoxetine treatment increased hippocampal MR and GR mRNAs and MR binding sites while GR number remained unchanged. In ADX rats supplemented with corticosterone, 5-HTP and fluoxetine treatment had the same effects on corticosteroid receptors compared to those observed in non supplemented ADX rats: 5-HTP decreased hippocampal MR and GR and hypothalamic GR while fluoxetine treatment increased hippocampal MR. These results show that short-term stimulation of 5-HT transmission by 5-HTP decreases hippocampal and hypothalamic corticosteroid receptor numbers through a corticosterone-independent mechanism. It is hypothesized that the delayed maximal increase in extracellular 5-HT contents after fluoxetine treatment, due to negative feedback regulations induced by the activation of 5-HT1A and 5-HT1B autoreceptors, is not the primary cause for the delayed normalization of corticosteroid receptor numbers that regulates the HPA axis functioning.

SSRIs
5-HTP
HPA axis
Corticosteroids
Fluoxetine and PMT
Prozac for tiny tots?
Fluoxetine and MDMA
Fluoxetine and MAO-A
Fluoxetine and MAO-B
Fluoxetine and weight
Fluoxetine and bipolars
Fluoxetine and oxytocin
Fluoxetine : side-effects
Imipramine versus fluoxetine
Hormones, the brain and stress
Fluoxetine: norepinephrine, dopamine and 5-HT2c
Tryptophan and 5-hydroxytryptophan for depression

Refs
HOME
HedWeb
Future Opioids
BLTC Research
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family