ArticleNeuropsychiatric disease and treatment2021
(2R,6R)-Hydroxynorketamine Alleviates Electroconvulsive Shock-Induced Learning Impairment by Inhibiting Autophagy.
Article in Neuropsychiatric disease and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Contemporary in vivo rodent electroconvulsive therapy (ECT) models in translational depression research: a systematic review.Translational psychiatry · 2025Pooled it
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Crucial role of autophagy in propofol-treated neurological diseases: a comprehensive review.Frontiers in cellular neuroscience · 2023Review
- Target deconvolution studies of (2R,6R)-hydroxynorketamine: an elusive search.Molecular psychiatry · 2022Article
- (2R,6R)-hydroxynorketamine rapidly potentiates optically-evoked Schaffer collateral synaptic activity.Neuropharmacology · 2022Article
- Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.Nature communications · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLearning impairment after electroconvulsive therapy (ECT) is common. Ketamine, an anesthetic used for ECT, has been demonstrated to attenuate cognitive impairment after ECT. However, the mechanism by which ketamine occurs in this case is still unknown. We aimed to explore the role of ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] in the protection against learning impairment and investigate whether autophagy is involved in the protective effect. MATERIALS AND
methodsA rat depression model received electroconvulsive shock (ECS; simulated ECT in animal models) daily for 3 days. The Morris water maze was used to assess the spatial learning function of the rats. Western blotting was used to detect the expression of Beclin-1, light chain (LC)3-II/LC3-I, p62, mammalian target of rapamycin (mTOR), and p-mTOR in the hippocampus.
resultsThe escape latency for the maze in the ECS group was significantly longer than that in the sham ECS group (P=0.042). Meanwhile, the escape latency in the (2R,6R)-HNK+ECS group was significantly shorter than that in the ECS group (P=0.005). The LC3-II/LC3-I ratio and Beclin-1 expression level significantly increased, and the p62 expression level significantly decreased in the ECS group, compared with those in the sham ECS group (all P<0.001). The (2R,6R)-HNK+ECS group showed lower LC3-II/LC3-I ratio (P<0.001) and Beclin-1 expression level (P<0.001) and higher p62 (P<0.001) and p-mTOR expression levels (P=0.048) than did the ECS group. After small-molecule enhancer of rapamycin 28 (SMER28) administration, the role of (2R,6R)-HNK in protecting against learning impairment and inhibiting autophagy was abrogated, showing no difference in the escape latency; the difference in the LC3-II/LC3-I ratio and p62 expression level between the SMER28+(2R,6R)-HNK+ECS and ECS groups was not as significant as that between the (2R,6R)-HNK+ECS and ECS groups (P<0.05-0.01 vs P<0.001).
conclusion(2R,6R)-HNK yields cognitive protection by suppressing autophagy through the mTOR signaling pathway in the ECS-treated rat hippocampus.
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