Neurochemical Research

, Volume 25, Issue 9, pp 1199–1206

5-HT-HPA Interactions in Two Models of Transgenic Mice Relevant to Major Depression

  • Laurence Lanfumey
  • Clotilde Mannoury La Cour
  • Nicolas Froger
  • Michel Hamon
Article

DOI: 10.1023/A:1007683810230

Cite this article as:
Lanfumey, L., La Cour, C.M., Froger, N. et al. Neurochem Res (2000) 25: 1199. doi:10.1023/A:1007683810230

Abstract

Reciprocal interactions between central 5-HT system and hypothalamo-pituitary-adrenal (HPA) axis are of particular relevance with regard to depression, in which alterations of both systems have been evidenced. In order to further explore these interactions, two models of mutant mice have been used. They consisted of knock-out mice lacking the 5-HT transporter (5-HTT−/−) and of transgenic mice with impaired glucocorticoid receptor (GR-i) expression. Under control conditions, the functional properties of 5-HT1A autoreceptors in GR-i mice were as in their paired wild-type. However, both chronic stress and long term treatment with fluoxetine induced abnormal adaptive changes in 5-HT1A autoreceptor functioning in GR-i mice. On the other hand, a marked desensitization of 5-HT1A autoreceptors was found in 5-HTT−/− mice as compared with paired wild-type animals, and this phenomenon was further enhanced by exposure to stressful conditions. These data show that alterations of HPA axis at the gene level has consequences on 5-HT neurotransmission, and reciprocally, that 5-HTT knock-out affects HPA-dependent responses to stress.

Serotonin 5-HT1A autoreceptors corticosterone depressive disorders transgenic mice stress 

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Laurence Lanfumey
    • 1
  • Clotilde Mannoury La Cour
    • 2
  • Nicolas Froger
    • 2
  • Michel Hamon
    • 2
  1. 1.Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié SalpêtrièreINSERM U 288Paris Cedex 13France
  2. 2.Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié SalpêtrièreINSERM U 288Paris Cedex 13France

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