Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice.
Yonglai Zhang, Rui Sha, Kaiguo Wang, Hao Li, Bo Yan, Naibao Zhou
Molecular medicine reports May 1, 2018 DOI: 10.3892/mmr.2018.8700 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Tetrahydropalmatine |
| Topics | Ketamine Esketamine |
| Keywords | Tetrahydropalmatine Cytochrome c Phospholipase c-γ1 |
| Citations | 26 |
| Key findings | Tetrahydropalmatine protected against ketamine-induced learning and memory impairment in mice by reducing oxidative stress, inflammation, and apoptosis, and by modulating glial and neurotrophic factors. |
Abstract
Tetrahydropalmatine exerts numerous pharmacological activities, including analgesic and narcotic effects; anti-arrhythmic, blood pressure lowering and cardioprotective effects; protective effects against cerebral ischemia-reperfusion injury; inhibition of platelet aggregation; prevention of ulcerative diseases and inhibition of gastric acid secretion; antitumor effects; and beneficial effects on the withdrawal symptoms associated with drug addiction. The present study aimed to investigate the protective effects of tetrahydropalmatine against ketamine‑induced learning and memory impairment in mice. The Morris water maze test and open field test were used to analyzed learning and memory impairment in mice. ELISA kits and western blotting were used to analyze oxidative stress, inflammation factors, caspease‑3 and caspase‑9, iNOS, glial fibrillary acidic protein (GFAP), glial cell‑derived neurotrophic factor (GDNF), cytochrome c and phospholipase C (PLC)‑γ1 protein expression. The results demonstrated that tetrahydropalmatine treatment significantly decreased escape latency in the learning phase and increased the number of platform site crossings in ketamine‑induced mice. In addition, tetrahydropalmatine significantly inhibited oxidative stress, inflammation and acetylcholinesterase activity, and decreased acetylcholine levels in ketamine‑induced mice. Tetrahydropalmatine also suppressed iNOS protein expression, weakened caspase‑3 and caspase‑9 activation, inhibited nuclear factor‑κB, glial fibrillary acidic protein, cytochrome c and phospholipase C‑γ1 protein expression, and induced glial cell‑derived neurotrophic factor protein expression in ketamine‑induced mice. Taken together, these results indicated that tetrahydropalmatine may protect against ketamine‑induced learning and memory impairment in mice via antioxidative, anti‑inflammatory and anti‑apoptotic mechanisms. The present study provided an experimental basis for the clinical application of tetrahydropalmatine to reduce the severe side effects associated with ketamine therapy in future studies.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |