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Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice
Yan-Jiong Chen1, Yan-Ling Liu, Qing Zhong
1Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
Objective:
The purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.
Methods:
Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and hippocampus.
Results:
Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA+THP-treated mice than in MA-treated mice.
Conclusion:
Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.
Insights
Methamphetamine (MA) impairs spatial learning and memory in mice. Co-administration with tetrahydropalmatine (THP) prevents this impairment, likely by affecting ERK1/2 expression in the prefrontal cortex.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Methamphetamine (MA) abuse is a significant public health concern.
- Understanding the neurobiological mechanisms underlying MA-induced cognitive deficits is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of MA on spatial learning and memory in mice.
- To determine the role of tetrahydropalmatine (THP) in mitigating MA-induced cognitive impairments.
- To explore the involvement of extracellular signal-regulated protein kinase (ERK) signaling in these effects.
Main Methods:
- Male C57BL/6 mice were administered varying doses of MA and THP, alone or in combination.
- Spatial learning and memory were assessed using the Morris water maze.
- Western blot analysis was employed to measure ERK1/2 expression in the prefrontal cortex (PFC) and hippocampus.
Main Results:
- MA treatment significantly impaired spatial learning and memory, evidenced by increased escape latency and reduced platform crossings.
- MA administration led to decreased ERK1/2 expression in the PFC, but not the hippocampus.
- Co-administration of MA and THP significantly ameliorated the cognitive deficits induced by MA and normalized ERK1/2 expression in the PFC.
Conclusions:
- Repeated MA administration negatively affects spatial learning and memory in mice.
- THP co-administration effectively prevents MA-induced spatial cognitive impairments.
- The protective effects of THP may be mediated by the modulation of ERK1/2 signaling pathways in the PFC, suggesting a potential therapeutic strategy for MA abuse.
