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Background: Early life stress is correlated with escalated peril for anxiety, mood,
substance, impulse control and depressive disorders. Such disorders might spring from
chemical imbalance in brain. A well-grounded mouse prototype of childhood adversity
contributing to the everlasting behavioral changes in an individual would help
understand the mechanism underlying these adverse effects. Maternal deprivation is
frequently used paradigm of early neglect. Natriuretic peptides especially Atrial
Natriuretic Peptide (ANP) released from Atrial myocytes have significant anxiolytic
role corroborated by certain animal and human trails. The concentration of ANP has
been found to be elevated by Levothyroxine (LT4) which treats the adverse symptoms
of anxiety and depression.
Method and Results: In an attempt to contrive the paradigm of childhood adversity in
mouse models with everlasting impacts on behavior of balb/c mice, maternal
separation model followed by early weaning model were developed and behavioral
tests were performed 60 days following maternal separation followed by early weaning
(MSEW) paradigm for the validation of model. The experimental and control groups
were further divided into 3 groups: MSEW group with drug administration, MSEW
group with no drug administration and control group with no MSEW and no drug
administration. Following a 7 days administration of LT4 at the concentration of 15
micrograms per mice to MSEW group and one of the control groups, decline in
anxiety level in mice subjected to MSEW was observed in comparison to the MSEW
group that was not administered LT4. These findings were validated by performing
anxiety related paradigms after drug injection and the difference in the behavior was
observed accordingly which suggested decrease in behavioral despair and anxiety
related symptoms in mice.
Conclusion: Our findings elucidate that maternal separation model followed by early
weaning contributes as a substantial paradigm to scrutinize the intricate behavioral
anomalies in organisms with early life adversity history and by increasing the
concentration of ANP by injection of LT4 cures the anxiety-related symptoms and
provides a n apprehension for a futuristic therapeutic plan of actions.