Abstract
Ketamine has become a popular recreational drug due to its neuronal anesthesia effect and low price. The process of learning and memory is part of the distinctive high-level neural activities in animals. We investigated the effects of subanesthetic and anesthetic doses of ketamine on the learning and memory-related signal transduction mechanisms. We used the Morris water maze test to execute rats’ learning and memory ability and detected changes of Arc mRNA and Arc, cAMP-response element-binding protein (CREB), phospho-CREB (p-CREB), extracellular signal-regulated kinase (ERK), and phospho-ERK (p-ERK) protein expression in the hippocampus 10 min and 24 h after administration. Ten min after ketamine injection, the Arc gene and the protein expression levels increased in all groups; p-ERK only increased in the chronic subanesthetic dose group. After 24 h, the Arc gene and the protein expression levels of the subanesthetic dose group increased, but those of the chronic subanesthetic dose group and anesthetic dose group decreased. However, p-ERK increased in all groups. A chronic subanesthetic dose of ketamine could increase learning and memory ability through ERK, CREB, and Arc in a short time, and the high body temperature after the subanesthetic dose of ketamine injection was the main factor leading to changes in Arc. The subanesthetic dose of ketamine regulated learning and memory through ERK, CREB, and ARC 24 h after injection.
Highlights
IntroductionIt is clinically used as an anesthetic for surgery or anesthesia inducer
Theofeffects of ketamine learning and memory in rats are shown in Morris water spatial learning and memory in rats are shown in Figure 1 and Table 2
After continuous administration of a stimulant dose of ketamine for 20 days, we found that 10 min after administration, p-extracellular signal-regulated kinase (ERK), p-cAMP-response element-binding protein (CREB), and Arc were positively correlated
Summary
It is clinically used as an anesthetic for surgery or anesthesia inducer. It has a certain mental dependence and impact on learning and memory [1,2]. Ketamine has an anesthetic effect at high doses (>80 mg/kg), but the drug can cause DNA damage in rodent models within 12 h [3]. At low doses, it can simulate an analgesic effect. Ketamine can be used as an analgesic after surgery [4]. Considering that ketamine has hallucinogenic and addictive properties, it often appears in various entertainment venues and has become a substance that is increasingly abused [5,6]
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