Synergistic antidepressant effects of citalopram and SB-334867 in the REM sleep-deprived mice: Possible role of BDNF

This study was done to evaluate the effect of co-treatment of orexin agents along with citalopram on the modulation of depression-like behavior and the expression of BDNF in the prefrontal cortex (PFC) of sleep -deprived male mice. A sleep deprivation model was performed in which rapid eye movement (REM) sleep was completely prohibited, and non-REM sleep was intensely reduced for 24 h. For drug microinjection, the guide cannula was surgically fixed in the left lateral ventricle of mice. Furthermore, we used the open-field test (OFT), forced swim test (FST), tail suspension test (TST), and splash test for recording depression-like behavior as well as Real-Time PCR amplification for assessing the expression of BDNF in the PFC of REM sleep-deprived mice. Our results revealed that REM sleep deprivation did not change locomotor activity while increased depressive -like behavior in FST, TST, and splash tests. However, the expression of BDNF was decreased in the PFC. Intra-peritoneally (i.p.) administration of citalopram induced antidepressant effect in the normal and REM sleep -deprived mice. Moreover, intracerebroventricular (i.c.v.) microinjection of a non-effective dose of SB-334867, an orexin antagonist, potentiated the antidepressant-like effect of citalopram. On the other hand, a non-significant dosage of orexin-1 reversed the antidepressant effect of citalopram in the normal and REM sleep-deprived animals. Furthermore, our results showed that injection of citalopram alone or with SB-334867 increased the mRNA expression level of BDNF in the PFC of REM sleep-deprived mice. These data suggest that REM sleep deprivation interferes with the neural systems underlying the depression-like process and supports a likely interaction of the orexin system with citalopram on the modulation of depression-like behavior in REM sleep-deprived mice.

Automated summary

This study evaluated the effects of co-treatment of orexin agents and citalopram on depression-like behavior and BDNF expression in the prefrontal cortex (PFC) of sleep-deprived male mice. It was found that sleep deprivation increased depression-like behavior while decreasing BDNF expression. Citalopram showed an antidepressant effect, which was potentiated by an orexin antagonist and reversed by orexin-1. The study suggests that the orexin system interacts with citalopram to modulate depression-like behavior in sleep-deprived mice.