Central 5-HT 1 and 5-HT 2 binding sites in transgenic mice with reduced glucocorticoid receptor number

Central 5-HT 1 and 5-HT 2 binding sites in transgenic mice with reduced glucocorticoid receptor... Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA, which partially blocks glucocorticoid receptor expression, were used in order to clarify the role of glucocorticoid receptors in the regulation of 5-HT 1A , 5-HT 1nonA and 5-HT 2 binding sites labelled by quantitative autoradiography in the frontal and prefrontal cortex, striatum, hypothalamus, amygdala and raphe nuclei. We found that 1 nM ( 3 H)8-hydroxy-2-(di- N -propylamino)tetralin (( 3 H)8-OH-DPAT) binding to 5-HT 1A sites was decreased in strata oriens (−15.1±3.5%) and radiatum–lacunosum–moleculare (−13.3±4.3%) of the hippocampal CA 3 area, and 2 nM ( 3 H)5-hydroxytryptamine binding to 5-HT 1nonA sites in the presence of 100 nM 8-OH-DPAT and mesulergine was decreased in the dorsal subiculum (−17.8±6.9%). By contrast, 5-HT 2 sites labelled by 0.5 nM of (±)-1-(2,5-dimethoxy-4-( 125 I)iodophenyl)-2-aminopropane was increased in the dorsal subiculum (+35.2±11.5%) and CA 2 area (+29.2±11.3%). The observed differences in binding to 5-HT 1 and 5-HT 2 sites were all located in areas of the hippocampus that contain both gluco- and mineralo-corticoid receptors, and no difference was observed in anatomical structures which contain only glucocorticoid receptors. Therefore, it seems that the important factor for the regulation of these 5-HT receptors is the interaction between gluco- and mineralo-corticoid receptors rather than the absolute density of glucocorticoid receptors. These results suggest that some of the alterations of the serotonergic neurotransmission observed in depressed patients might be secondary to an altered glucocorticoid receptor function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Central 5-HT 1 and 5-HT 2 binding sites in transgenic mice with reduced glucocorticoid receptor number

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science B.V.
ISSN
0006-8993
DOI
10.1016/S0006-8993(00)02104-1
Publisher site
See Article on Publisher Site

Abstract

Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA, which partially blocks glucocorticoid receptor expression, were used in order to clarify the role of glucocorticoid receptors in the regulation of 5-HT 1A , 5-HT 1nonA and 5-HT 2 binding sites labelled by quantitative autoradiography in the frontal and prefrontal cortex, striatum, hypothalamus, amygdala and raphe nuclei. We found that 1 nM ( 3 H)8-hydroxy-2-(di- N -propylamino)tetralin (( 3 H)8-OH-DPAT) binding to 5-HT 1A sites was decreased in strata oriens (−15.1±3.5%) and radiatum–lacunosum–moleculare (−13.3±4.3%) of the hippocampal CA 3 area, and 2 nM ( 3 H)5-hydroxytryptamine binding to 5-HT 1nonA sites in the presence of 100 nM 8-OH-DPAT and mesulergine was decreased in the dorsal subiculum (−17.8±6.9%). By contrast, 5-HT 2 sites labelled by 0.5 nM of (±)-1-(2,5-dimethoxy-4-( 125 I)iodophenyl)-2-aminopropane was increased in the dorsal subiculum (+35.2±11.5%) and CA 2 area (+29.2±11.3%). The observed differences in binding to 5-HT 1 and 5-HT 2 sites were all located in areas of the hippocampus that contain both gluco- and mineralo-corticoid receptors, and no difference was observed in anatomical structures which contain only glucocorticoid receptors. Therefore, it seems that the important factor for the regulation of these 5-HT receptors is the interaction between gluco- and mineralo-corticoid receptors rather than the absolute density of glucocorticoid receptors. These results suggest that some of the alterations of the serotonergic neurotransmission observed in depressed patients might be secondary to an altered glucocorticoid receptor function.

Journal

Brain ResearchElsevier

Published: Apr 17, 2000

References

  • Effects of stress on the functional properties of pre-and postsynaptic 5-HT 1B receptors in the rat brain
    Bolanos-Jimenez, F.; Manahaes de Castro, R.M.; Seguin, L.; Cloez-Tayarani, I.; Monneret, V.; Drieu, K.; Fillion, G.
  • Blockade of corticosterone synthesis reduces serotonin turnover in the dorsal hippocampus of the rat as measured by microdialysis
    Korte-Bouws, G.A.; Korte, S.M.; de Kloet, E.R.; Bohus, B.
  • Effect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT receptor binding sites in neocortex of rat forebrain and 5-HT 2 receptor-mediated wet-dog shake behaviors
    Kuroda, Y.; Mikuni, M.; Ogawa, T.; Takahashi, K.
  • Glucocorticoid receptor-mediated inhibition by corticosterone of 5-HT 1A autoreceptor functioning in the rat dorsal raphe nucleus
    Laaris, N.; Haj-Danhmane, S.; Hamon, M.; Lanfumey, L.
  • Agonist-and antagonist-induced plasticity of rat 5-HT 1A receptor in hippocampal cell culture
    Nishi, M.; Azmitia, E.C.
  • Flesinoxan treatment reduces 5-HT 1A receptor mRNA in the dentate gyrus independently of high plasma corticosterone levels
    Sibug, R.M.; Compaan, J.C.; Meijer, O.C.; Van der Gugten, J.; Olivier, B.; De Kloet, E.R.

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