Anti-ceramidase LCL385 acutely reduces BCL-2 expression in the hippocampus but is not associated with an increase of learned helplessness in rats

Ziad Nahas, Yan Jiang, Youssef H. Zeidan, Alicja Bielawska, Zdzislaw Szulc, Lindsay DeVane, Peter Kalivas, Yusuf A. Hannun

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Evidence from in situ studies supports the role of anti-apoptotic factors in the antidepressant responses of certain psychotropics. The availability of anti-ceramidase pro-apoptocic compound (LCL385) provides an opportunity to test in vivo the relation between hippocampal apopotosis and learned helplessness. Method: 40 Sprague-Dawley male rodents underwent an FST after a treatment with LCL385, desipramine (DMI), or placebo (SAL) over 3 days. Behavioral responses, including immobility, swimming and climbing were counted during the 6 min test. Western blot labeling was used to detect anti-apoptosis in hippocampus. Results: DMI alone was associated with reduced immobility and increased climbing whereas LCL385 alone showed a decrease in Bcl-2/β-actin ratio. Conclusions: Direct modulation of Bcl-2 expression in the hippocampus is not associated with learned helplessness in stressed rats. Three-day administration of DMI and LCL385 show divergent effects on behavioral and anti-apoptotic measures.

Original languageEnglish (US)
Pages (from-to)41-44
Number of pages4
JournalBehavioural Brain Research
Volume197
Issue number1
DOIs
StatePublished - Jan 30 2009
Externally publishedYes

Bibliographical note

Funding Information:
This project was funded by K08 MH070615-01A1 (ZN) and through general funds from the Department of Cell Biology, the Department of Neurosciences, the Laboratory of Drug Disposition & Pharmacogenetics, the Brain Stimulation Laboratory and the Mood Disorders Program at MUSC. The authors would like to thank Bill Carlezon and Irvin Lucki for their input on the behavioral paradigms, Professor Jacqueline McGinty for advise on Western Blot analyses, Saeed Elojeimy for discussing LCL385 early behavioral effects and lethal doses and Aram Parsegian for scoring the FST.

Keywords

  • Apoptosis
  • Bcl-2
  • Ceramide
  • Depression
  • Despair
  • FST
  • Helplessness
  • Hippocampus
  • Rodent
  • Stress

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