Grants and Contracts Details
Description
--The primary objective of this proposal is to test the hypothesis that: corticosterone
exposure potentiates ethanol withdrawal (EWD)-induced toxicity. The primary aim of
this proposal will be achieved by:
1. Determining the effects of corticosterone exposure during ethanol exposure
and/or withdrawal from chronic ethanol exposure on toxicity utilizing organotypic
hippocampal slice cultures from neonatal rat brain.
The aim of this set of experiments was to characterize the effects of
corticosterone (CORT) exposure during the withdrawal period from la-day ethanol
exposure. We chose an ethanol treatment regiment that itself does not cause
significant cytotoxicity upon withdrawal (i.e. 50 roM) and non-toxic CORT
concentrations. When CORT was exposed to cultures at the initiation of ethanol
withdrawal, a concentration-dependent effect was observed. In the CA1 region, 0.1 uM
CORT increased cytotoxicity above control cultures and cultures withdrawn from la-day
ethanol exposure. In cultures treated with 1.0 uM CORT during the withdrawal period,
a significant increase in cytotoxicity was observed above cultures treated with 0.1
uM CORT during EWD. In addition, 1.0 uM CORT exposure during EWD resulted in
significant cytotoxicity in the dentate gyrus, an effect that was not observed at any
other CORT concentration or in cultures withdrawn from ethanol. An attenuation of
cytotoxicity induced by CORT and EWD was observed in cultures treated with 20 uM
MK-B01 during the withdrawal period.
In the final set of experiments, we exposed cultures to 50 roM ethanol for 10 days
and withdrew them for 1-day. Addition cultures were exposed to 1.0 uM CORT during
ethanol treatment and during the 1-day withdrawal period. We observed a significant
increase in toxicity in each hippocampal sub-region in cultures treated with 1.0 uM
CORT during ethanol exposure and withdrawal, with the CAl region being most sensitive
to the cytotoxic effects of CORT and ethanol exposure. MK-B01 exposure during the
withdrawal period reduced the cytotoxicity associated with CORT exposure and EWD.
13. SUMMARY OF ACTIVITIES (Do not exceed 3 pages.)
A. CHANGES
Since submission of the last application/progress report, have any significant changes occurred in the training program,
particularly the research project, academic status, or time distribution of activities (Le., percentage of time devoted to
research project, course work, teaching, etc.)? If so, explain.
B. PROGRESS
Describe concisely the research performed and research training obtained during the past year. List all courses and
publications. Complete the Gender and Minority Inclusion table(s) (see below), if applicable.
C. RESEARCH TRAINING PLANS
Describe concisely the research and research training planned for the requested budget period, including any course work.
A. CHANGES
none
B. PROGRESS
The primary objective of this proposal is to test the hypothesis that: corticosterone
exposure potentiates ethanol withdrawal (EWD)-induced toxicity. The primary aim of
this proposal will be achieved by:
1. Determining the effects of corticosterone exposure during ethanol exposure
and/or withdrawal from chronic ethanol exposure on toxicity utilizing organotypic
hippocampal slice cultures from neonatal rat brain.
The aim of this set of experiments was to characterize the effects of
corticosterone (CORT) exposure during the withdrawal period from lO-day ethanol
exposure. We chose an ethanol treatment regiment that itself does not cause
significant cytotoxicity upon withdrawal (i.e. 50 roM) and non-toxic CORT
concentrations. When CORT was exposed to cultures at the initiation of ethanol
withdrawal, a concentration-dependent effect was observed. In the CA1 region, 0.1 uM
CORT increased cytotoxicity above control cultures and cultures withdrawn from 10-day
ethanol exposure. In cultures treated with 1.0 uM CORT during the withdrawal period,
a significant increase in cytotoxicity was observed above cultures treated with 0.1
uM CORT during EWD. In addition, 1.0 uM CORT exposure during EWD resulted ih
significant cytotoxicity in the dentate gyrus, an effect that was not observed at any
other CORT concentration or in cultures withdrawn from ethanol. An attenuation of
cytotoxicity induced by CORT and EWD was observed in cultures treated with 20 uM
MK-801 during the withdrawal period.
In the final set of experiments, we exposed cultures to 50 roM ethanol for 10 days
and withdrew them for 1-day. Addition cultures were exposed to 1.0 uM CORT during
ethanol treatment and during the 1-day withdrawal period. We observed a significant
increase in toxicity in each hippocampal sub-region in cultures treated with 1.0 uM
CORT during ethanol exposure and withdrawal, with the CA1 region being most sensitive
to the cytotoxic effects of CORT and ethanol exposure. MK-801 exposure during the
withdrawal period reduced the cytotoxicity associated with CORT exposure and EWD.
Status | Finished |
---|---|
Effective start/end date | 9/30/03 → 9/29/05 |
Funding
- National Institute on Alcohol Abuse and Alcoholism: $27,832.00
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