Antidepressant-like effects of sodium butyrate in combination with estrogen in rat forced swimming test: Involvement of 5-HT1A receptors

Sodium butyrate (NaB), a histone deacetylase inhibitor, has been implicated in the antidepressant-like effects either injected as a single drug or in combination with selective serotonin reuptake inhibitor (SSRI), such as fluoxetine. Estrogen is also demonstrated to have antidepressant effect especially together with fluoxetine. We investigated whether NaB administered in combination with estradiol benzoate (EB) exerted antidepressant-like effect in forced swimming test (FST) in ovariectomized female rats. Furthermore, we detected the mRNA expressions of serotonin receptors and neuropeptides in hypothalamus, both of which participate in the mood disorder. Ovariectomized female SD rats were treated with vehicle, NaB, EB or NaB combined with EB for 7 days and then subjected to FST. The expressions of serotonin receptors (5-hydroxytryptamine receptor), corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the hypothalamus were detected by real time PCR. We found that co-treated with NaB and EB resulted in a significant decrease in immobility behavior in FST, a measure for depression-like behavioral. 5-HT1A antagonist, WAY 100635, significantly block the antidepressant-like effects induced by NaB plus EB. The mRNA expression of the serotonin-1A [5-hydroxytryptamine 1A (5-HT1A)] receptor was increased in the co-treated group in hypothalamus, while there was no difference in the mRNA expression of 5-HT2A or 5-HT2C. The mRNA expression of CRH or AVP was not significantly altered either. In conclusion, NaB may exert antidepressant-like effects in combination with EB in ovariectomized female rats through 5-HT1A receptor, via altering the expression of 5-HT1A in the hypothalamus.