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Effects of 5-HT2 receptor antagonist on cycloheximide-induced amnesia in mice
T Nabeshima1, K Itoh, K Kawashima
1Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences Meijo University, Nagoya, Japan.
Abstract:
A role played by serotonergic neuronal system in cycloheximide (CXM)-induced amnesia was studied in mice using a step-down passive avoidance task. CXM (30 mg/kg SC) given immediately after training caused impairment of memory. Nonselective serotonin (5-HT) antagonist methysergide and selective 5-HT2 antagonist ritanserin significantly attenuated impairment of memory caused by CXM. 5-HT1 antagonist (+/-)-pindolol had no effect on CXM-induced amnesia. The antiamnesic effect of ritanserin on CXM-induced amnesia was antagonized by 5-HT (ICV), but not by nonselective 5-HT agonist 5-methoxy-N,N-dimethyltryptamine and 5-HT1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin at the dose level which did not cause the memory disruption. Scopolamine antagonized the antiamnesic effects of methysergide and ritanserin on CXM-induced amnesia. These results suggest that 5-HT2 receptors and cholinergic neuronal system may play an important role in memory formation.
Insights
Serotonin receptors influence memory. Blocking serotonin 5-HT2 receptors reversed cycloheximide-induced amnesia in mice, suggesting their role in memory formation.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The serotonergic system modulates cognitive functions, including memory.
- Cycloheximide (CXM) is a known amnesic agent used to study memory impairment.
Purpose of the Study:
- To investigate the role of the serotonergic system in cycloheximide-induced amnesia.
- To identify specific serotonin receptor subtypes involved in memory formation.
Main Methods:
- A step-down passive avoidance task was used in mice.
- Memory impairment was induced using cycloheximide (CXM).
- The effects of various serotonin antagonists and agonists were evaluated.
Main Results:
- CXM administration impaired memory retention.
- Methysergide (nonselective 5-HT antagonist) and ritanserin (selective 5-HT2 antagonist) attenuated CXM-induced amnesia.
- (+/-)-Pindolol (5-HT1 antagonist) had no effect.
- The antiamnesic effect of ritanserin was blocked by 5-HT but not by other serotonin agonists.
- Scopolamine blocked the antiamnesic effects of methysergide and ritanserin.
Conclusions:
- Serotonin 5-HT2 receptors play a significant role in memory formation.
- The cholinergic system interacts with the serotonergic system in memory processes.