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


METHODS
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 6min 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/beta-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.
Nahas
Ziad
Z
Mood Disorders Program, University of South Carolina, Charleston, SC 29425, USA.
Jiang
Yan
Y
Zeidan
Youssef H
YH
Bielawska
Alicja
A
Szulc
Zdzislaw
Z
Devane
Lindsay
L
Kalivas
Peter
P
Hannun
Yusuf A
YA