Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju.

Accumulating evidence indicated that Nmethyl-D-aspartate (NMDA) receptors are involved in the
pathophysiology of depression and implicated in therapeutic targets. NMDA antagonists, such as ketamine, displayed fast-onset and long-lasting antidepressant activity in
preclinical and clinical studies. Previous studies showed
that Yueju pill exerts antidepressant effects similar to
ketamine. Here, we focused on investigating the association of acute and lasting antidepressant responses of Yueju
with time course changes of NMDA receptor subunits
NR1, NR2A, and NR2B expressions in the hippocampus, a
key region regulating depression response. As a result,
Yueju reduced immobility time in the forced swimming
test from 30 min to 5 days post a single administration.
Yueju acutely decreased NR1 and NR2B protein expression in the hippocampus, with NR2A expression unaltered.
NR1 expression remained down-regulated 5 days post
Yueju administration, whereas NR2B returned to normal
level in 24 h. Yueju and ketamine similarly ameliorated the
depression-like symptoms at least for 72 h in learned
helplessness test. They both reversed the up-regulated
expression of NR1 in the learned helpless mice 1 or 3 days
post administration. Different from ketamine, the antidepressant effects of Yueju were not influenced by blockade
of amino-3-hydroxy-5-methyl-4-isoxazole propionate
receptor. These findings served as preclinical evidence that
Yueju may confer acute and long-lasting antidepressant
effects by favorably modulating NMDA function in the
hippocampus.