Objective:

2

To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits.

Methods:

2

The male C57BL/6J mice were assigned to 4 groups using the complete randomization method

including control (CON

n

=19)

CRS (

n

=19)

SZRD (

n

=21)

and fluoxetine (Flu

n

=22) groups. Mice were restrained for 6 h per day

over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily

respectively

30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evalu

ated using behavioral tests including the tail suspension test

elevated plus maze test

and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence

while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings.

Results:

2

SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (

P

<

0.05 or

P

<

0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (

P

<

0.01). Additionally

SZRD selectively attenuated excitatory (

P

<

0.01)

but not inhibitory

synaptic transmission onto BLA pyramidal neurons.

Conclusion:

2

SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.