The role of 5-HT4 serotonin receptors in the CA1 hippocampal region on memory acquisition impairment induced by total (TSD) and REM sleep deprivation (RSD)

Sleep is a circadian rhythm that is modulated by endogenous circadian clock located in the suprachiasmatic nucleus (SCN). Sleep modulates memory acquisition and promotes memory consolidation. Studies have shown that sleep deprivation (SD) impairs different types of memory including passive avoidance. Furthermore, the hippocampus plays a significant role in modulating passive avoidance memory. On the other hand, 5-HT4 receptors are expressed in the hippocampus and involved in learning and memory processes. In this study, we aimed to investigate the role of CA1 hippocampal 5-HT4 receptors in memory acquisition impairment induced by total sleep deprivation (TSD: 24 h) and REM sleep deprivation (RSD: 24 h). The water box apparatus was used to induce TSD, while multi-platform apparatus was applied to induce RSD. Passive avoidance memory test was also used to evaluate memory acquisition. The results showed that, intra-CA1 pre-training injection of RS67333 (5-HT4 agonist) and RS23597 (5-HT4 antagonist) at the doses of 0.01 and 0.1 µg/rat decreased memory acquisition, but did not alter pain perception and locomotor activity. Furthermore, TSD and RSD decreased memory acquisition; however, only TSD decreased locomotor activity and induced analgesic effect. The sub-threshold doses of RS67333 and RS23597, 0.001 and 0.0001 µg/rat, respectively, reversed the effect of TSD on memory acquisition and locomotor activity. In addition, only RS23597 reversed TSD-induced analgesia. In RSD condition, the subthreshold dose of RS23597 improved RSD-induced memory acquisition deficit. In conclusion, CA1 hippocampal 5-HT4 receptors play an important role in TSD/RSD-induced cognitive alterations.