Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc

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.

Global Proteomic Profile of Aluminum-Induced Hippocampal Impairments in Rats: Are Low Doses of Aluminum Really Safe?

“…A factor that must be taken into account in proteomics studies is the action of anesthesia on protein expression. Both in vitro and in vivo studies demonstrate that prolonged action of anesthetics (i.e., ketamine, propofol, dexmedetomidine) modifies proteomics, ultimately leading to differential protein expression [ 55 , 56 , 57 , 58 , 59 ], with different types of anesthesia resulting in differential effects in distinct regions of the brain, including the hippocampus [ 59 , 60 , 61 , 62 ]. The use of anesthesia aimed at euthanasia has a varied effect depending on the anesthetic used and the protein analyzed, for instance, not resulting in a significant impact on MAP kinase protein expression [ 60 ].…”

Euonymus alatus Twig Extract Protects against Scopolamine-Induced Changes in Brain and Brain-Derived Cells via Cholinergic and BDNF Pathways

“…The binding of BDNF to its receptor, tropomyosin-related kinase B (TrkB), initiates numerous signaling pathways, including phosphorylation of CREB followed by direct activation of CREB-dependent transcription and further gene expression of BDNF [ 11 ]. Further activation of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase family, can lead to improvements in cognitive abilities as it can activate CREB and further regulate numerous neuronal processes, including learning and memory formation [ 12 , 13 ]. These signaling molecules are also regulated by neurotransmitters and hormones like acetylcholine (ACh).…”

The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms

“…In addition, no significant between-group difference was found regarding the level of CREB expression ( Figure 5 B). Several studies have illustrated that CREB mobilisation is dependent on phosphorylation at the Ser133 site, which is widely involved in many forms of neuronal activity: synaptic plasticity, learning, and memory [ 53 , 54 ]. Lv et al identified that Arc is the critical downstream molecule of the extracellular signal-related kinase (ERK)-CREB pathway [ 55 ].…”