Expression of genes encoding cytokines and corticotropin releasing factor are altered by citalopram in the hypothalamus of post-stroke depression rats.

OBJECTIVES

To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats.

METHODS

Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated.

RESULTS

MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1β and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1β mRNA levels in the citalopram-treated group of rats.

CONCLUSION

The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1β transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy.