Objective       To determine the expression alteration of corticotrophin-releasing factor (CRF) mRNA in the hypothalamus of serotonin transporter (SERT)-knockout mice exposed to elevated plus maze (EPM).        Methods       Mice were divided into 2 groups

a control group and an EPM group

according their genotypes (SERT

+/+

SERT

+/-

and SERT

-/-

)

with 10 mice in each group. EPM was used as a stressor to stimulate the

mice. Then anxious like behavior was observed

and the CRF mRNA expression in the hypothalamus and nucleus paraventricularis (PVN) were measured.        Results       The non-stress expression of CRF mRNA in the hypothalamus and PVN were lower in both SERT

+/-

and SERT

-/-

mice than in SERT

+/+

mice (P0.05). Exposure to the EPM significantly increased CFR mRNA in the hypothalamus and PVN of SERT

+/-

and SERT

-/-

mice (P0.05)

higher than that of the SERT

+/+

mice. CRF mRNA antisense probes in the PVN detected high density of CRF mRNA

but CRF sense mRNA did not. With exposure to the EPM

the expression of hnRNA in SERT

-/ -

mice was significantly higher than that in the control group (P0.01).        Conclusion       Stress from exposure to EPM significantly increases CRF mRNA expression in the PVN and hypothalamus of SERT

+/-

and SERT

-/-

mice. The abnormal stress reaction of SERT-knockout mice is associated with the increased CRF mRNA expression.