Abstract
BACKGROUND: Serotonin receptors such as 5-HT3 plays critical role in regulation of sleep, wake cycle and cognitive process. Thus, we investigated the role of CA1 5-HT3 serotonin receptors in memory acquisition deficit 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: Modified water box and multi-platform apparatus were used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open field 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 5HT3 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 deficit 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.