Anhedonia Was Associated with the Dysregulation of Hippocampal HTR4 and MicroRNA Let-7a in Rats

Objective: Depression is a serious mental illness. However, the molecular mechanisms responsible for the development of depression remain unknown.

Methods: In this study, animal models of depression were established using maternal deprivation (MD) and chronic unpredictable stress (CUPS). Behavioral performance of rats was monitored by open field test, forced swim test, and sucrose consumption test. The expression of serotonin receptor-4 (Htr4) mRNA and Let-7a microRNA was detected by real-time PCR, while Htr4 protein level was measured by Western blot.

Results: In the open field test, rats subjected to MD and CUPS exhibited significant decreases in vertical activity. CUPS rats spent less time in the central area and excreted more fecal pellets than MD and control rats. In the forced swim and sucrose consumption tests, CUPS and MD rats exhibited significantly longer floating time and consumed less sucrose than control rats. MD rats exhibited significantly shorter floating time and consumed less sucrose than CUPS rats. MD rats showed significantly lower Htr4 mRNA and protein expression and significantly higher Let-7a level in the hippocampus than control rats. Htr4 mRNA and protein expression negatively correlated with Let-7a expression. Htr4 mRNA expression positively correlated with sucrose preference rate, while Let-7a expression negatively correlated with the sucrose preference rate.

Conclusion: Anhedonia, not despair or a decline in exploratory interest, may be associated with upregulation of Let-7a and downregulation of Htr4 expression in the hippocampus. The hippocampal Htr4 level may be regulated by Let-7a in rats.