Stress-induced behavioral depression in the rat is
associated with a decrease in GABA receptor-mediated
chloride ion flux and brain benzodiazepine receptor
occupancy.
Drugan
RC, Morrow AL, Weizman R, Weizman A,
Deutsch SI, Crawley JN, Paul SM.
Clinical
Neuroscience Branch, National Institute of Mental
Health, Bethesda, MD 20892.
Rats exposed to
inescapable tailshock exhibit deficits in learning a
simple shuttlebox escape task 24 h later. This syndrome
has been termed 'behavioral depression' or 'learned
helplessness', and is a model of stress-induced
depression. In the present study a significant (25%)
decrease in GABA receptor-mediated chloride ion flux as
measured by muscimol-stimulated 36Cl- uptake in
synaptoneurosomes was found in the cerebral cortices of
rats that failed the shuttlebox task as compared to
naive control rats. Rats which were exposed to tailshock
and subsequently learned the escape task did not show a
significant difference in muscimol-stimulated 36Cl-
uptake as compared to naive control rats. Similarly,
rats that failed to learn the shuttlebox escape task had
significantly lower in vivo [3H]Ro15-1788 specific
binding in cerebral cortex (43%), hippocampus (35%) and
striatum (33%) as compared to naive control rats. In
cerebellum and hypothalamus, there were significant
reductions in specific [3H]Ro15-1788 binding in both
animals that failed and animals that learned the
shuttlebox escape task as compared to naive controls. To
control the stress of the footshock associated with the
shuttlebox escape task, we investigated the effect of
gridshock in which total footshock received was
equivalent to that received by rats who failed the
shuttlebox task. There were no differences in muscimol-stimulated
36Cl- uptake or in vivo [3H]Ro15-1788 specific binding
between naive controls and rats administered footshock
independent of a learning task. These data suggest that
the development of stress-induced behavioral depression
may be associated with a decrease in GABA
receptor-mediated chloride channel function.
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