Background
Postmortem studies have repeatedly found decreased density and number of glia in cortical
regions, including the prefrontal and cingulate areas, from depressed patients. However,
it is unclear whether this glial loss plays a direct role in the expression of depressive
symptoms.
Methods
To address this question, we characterized the effects of pharmacologic glial ablation
in the prefrontal cortex (PFC) of adult rats on behavioral tests known to be affected
by stress or antidepressant treatments: sucrose preference test (SPT), novelty suppressed
feeding test (NSFT), forced swim test (FST), and two-way active avoidance test (AAT).
We established the dose and time course for the actions of an astrocyte specific toxin,
L-alpha-aminoadipic acid (L-AAA), and compared the behavioral effects of this gliotoxin
with the effects of an excitotoxic (ibotenate) lesion and to the effects of chronic
stress.
Results
The results demonstrate that L-AAA infusions induced anhedonia in SPT, anxiety in
NSFT, and helplessness in FST and AAT. These effects of L-AAA were similar to chronic
unpredictable stress (CUS)-induced depressive-like behaviors in these tests. However,
ibotenate-induced neurotoxic lesion of the PFC had no effect in these behavioral tests.
Conclusions
The results demonstrate that glial ablation in the PFC is sufficient to induce depressive-like
behaviors similar to chronic stress and support the hypothesis that loss of glia contributes
to the core symptoms of depression.
Key Words
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Article info
Publication history
Published online: July 21, 2008
Accepted:
June 12,
2008
Received in revised form:
May 16,
2008
Received:
August 29,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
