Different Role of CA1 5HT3 Serotonin Receptors on Memory Acquisition Deficit Induced by Total (TSD) and REM Sleep Deprivation (RSD)

Background: Serotonin receptors such as 5-HT3 plays critical role in regulation of sleep, 􀁚􀁄􀁎􀁈 cycle and cognitive process. Thus, we investigated the role of CA1 5HT3 serotonin receptors in memory acquisition 􀁇􀁈􀂿􀁆􀁌􀁗 induced by total sleep deprivation (TSD; for 24 hour) and REM sleep deprivation (RSD; for 24 hour). Pain perception and locomotor activity were also assessed as factors that may affect the memory process. Methods: 􀀰􀁒􀁇􀁌􀂿􀁈􀁇 water box and multi-platform apparatus were used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open 􀂿􀁈􀁏􀁇 devices were used for assessment of memory acquisition, pain and locomotor activity, respectively. Results: Totally, 152 male Wistar rats were used in the study. Pre-training, intra-CA1 injection of 5-HT3 receptor agonist Chlorophenylbiguanide (Mchl; 0.01 and 0.001 μg/rat; P < 0.001) and antagonist Y-25130 (0.1 μg/rat; P < 0.001) reduced memory acquisition and did not alter pain response, while higher dose of both drugs increased locomotor activity in normal rats. Both TSD and RSD reduced memory acquisition (P < 0.001) and did not alter locomotor activity, while TSD (P < 0.001) but not RSD induced analgesia effect. The amnesia induced by TSD was restored by subthreshold dose of Y25130 (0.001 μg/rat; P < 0.001) but not Mchl (0.0001 μg/rat), while both drugs reversed TSD-induced analgesia effect (P < 0.01 for Mchl and P < 0.05 for Y25130), and Y25130 increased locomotor activity in TSD rats (P < 0.05). In RSD rats, subthreshold dose of both drugs did not alter memory acquisition 􀁇􀁈􀂿􀁆􀁌􀁗 and increased locomotor activity (P < 0.001 for Mchl and P < 0.01 for Y25130), while the Y25130 (P < 0.001), but not Mchl induced analgesia in the RSD rats. Conclusion: Based on the above data, CA1 5HT3 receptors seem to play a critical role in cognitive and non-cognitive behaviors induced by TSD and RSD.