Objective: Under physiological conditions, astrocytes produce lactate to meet
the increased synaptic energy demand due to neuronal activity. In the light
of the findings showing that this process is disrupted in the pathophysiology
of major depression, the aim of this study is to investigate the effect of
pharmacological inhibition of perisynaptic astrocyte glycogen utilization on
anxiety-like behavior and depression-like behavior in female and male mice.
Methods: In this study, DAB (1,4-dideoxy-1,4-imino-D-arabinitol), which
is an inhibitor of glycogen breaking enzyme glycogen phosphorylase,
was intrahippocampally administered to 15 female and 14 male Swiss
albino mice, while 15 female and 12 male Swiss albino mice received
intrahippocampal saline injections. Three and five days after the injections,
the anxiety-like and depression-like behaviors of the mice were assessed by
locomotor activity, open-field test, light-dark box test, tail suspension test
and sucrose preference test.
Results: Three days after injection, neither depression-like nor anxietylike
significant behavioral changes were detected in the male experimental
group mice compared to the control group; but an increase in locomotor
activity (p=0.05) and time spent in the open-field (p=0.01) were observed
on the fifth day. In evaluations of the female experimental group mice on the
third and fifth days, depression-like and anxiety-like behaviors were found
similar to the control group, as seen in the male mice. The only significant
difference in the experimental group female mice was found in the sucrose
preference test, which revealed an increased tendency to prefer sucrose
(p=0.003) compared to the control group.
Conclusion: The inhibition of glycogen use in the hippocampus by DAB
did not affect anxiety-like and depression-like behaviors 3 and 5 days after
injection in both female and male mice. The increase in the time spent in the
open-field by male experimental group mice was associated not with anxiety,
but with increase in the locomotor activity. The fact that no significant
difference was observed in the light-dark box test, which is another test used
to evaluate anxiety, supported this opinion. The increase seen in the sucrose
preference test in female experimental group mice was not interpreted as an
increase in hedonic behavior because prevention of glycogen breakdown in
the hypothalamus might have homeostatically increased sugar-craving and
therefore resulted in an increase in sucrose preference. Different set of tests
better targeting the energy and glucose metabolism and applied at farther
time points than surgery are recommended for future studies.
Keywords: Glycogen, Depression-like Behavior, Anxiety-like Behavior