These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The 3beta-hydroxysteroid dehydrogenase inhibitor trilostane shows antidepressant properties in mice.
    Author: Espallergues J, Givalois L, Temsamani J, Laruelle C, Maurice T.
    Journal: Psychoneuroendocrinology; 2009 Jun; 34(5):644-59. PubMed ID: 19117688.
    Abstract:
    Changes in neuro(active)steroid levels are involved in depressive states and mood disorders. For instance, dehydroepiandrosterone or pregnenolone sulfate showed anti-stress and antidepressant activity in rodents and regulation of allopregnanolone levels appeared to be one of the consequence of an effective antidepressant therapy in patients. 4alpha,5-Epoxy-17beta-hydroxy-3-oxo-5alpha-androstane-2alpha-carbonitrile (trilostane) inhibits the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) that, in particular, converts pregnenolone into progesterone. We examined whether systemic administration of trilostane affects the response to stress and depression. An acute treatment with trilostane (6.3-50mg/kg SC injected twice -16 and -2h before the measure) increased 3beta-HSD mRNA levels in the hippocampus and adrenals, but had little effect on protein levels. The trilostane treatment failed to affect open-field, locomotor or exploratory behaviors, but significantly reduced the immobility duration in the forced swimming test, measuring antidepressant-like activity, and increased the time spent in open arm in the elevated plus-maze, measuring anxiety response. The antidepressant-like effect of trilostane was effective after a repeated treatment (2.5-20mg/kgSC twice-a-day during 7 days) or in mice submitted to a restraint stress during 21 days and showing several behavioral and physiological parameters of depression (decreased body weight, increased adrenal glands weight and anhaedonia). Trilostane also reduced stress-induced increase in plasma corticosterone and ACTH levels, showing direct effect on HPA axis activity. These observations suggest that the 3beta-HSD inhibitor trilostane present antidepressant-like activity, putatively by regulating brain and peripheral levels of neuroactive steroids.
    [Abstract] [Full Text] [Related] [New Search]