Potential mechanisms for phencyclidine/ketamine-induced brain structural alterations and behavioral consequences

Wang, Cheng; Inselman, Amy L.; Liu, Shuliang; Liu, Fang

doi:10.1016/j.neuro.2019.12.005

Cited by 9 publications

(4 citation statements)

References 136 publications

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“…(1) The strongest evidence for this hypothesis is that PCP and ketamine induce all symptoms in schizophrenia. However, the latest studies have revealed that PCP and ketamine do not function exclusively as NMDAR antagonists in the brain (Seillier and Giuffrida, 2009;Zanos and Gould, 2018;Fujigaki et al, 2019;Wang et al, 2020).…”

Section: The Possible Reasons For Unsatisfactory Clinical Resultsmentioning

confidence: 99%

Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia

Huang

2021

Front. Neurosci.

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Treatments for negative symptoms and cognitive dysfunction in schizophrenia remain issues that psychiatrists around the world are trying to solve. Their mechanisms may be associated with N-methyl-D-aspartate receptors (NMDARs). The NMDAR hypofunction hypothesis for schizophrenia was brought to the fore mainly based on the clinical effects of NMDAR antagonists and anti-NMDAR encephalitis pathology. Drugs targeted at augmenting NMDAR function in the brain seem to be promising in improving negative symptoms and cognitive dysfunction in patients with schizophrenia. In this review, we list NMDAR-targeted drugs and report on related clinical studies. We then summarize their effects on negative symptoms and cognitive dysfunction and analyze the unsatisfactory outcomes of these clinical studies according to the improved glutamate hypothesis that has been revealed in animal models. We aimed to provide perspectives for scientists who sought therapeutic strategies for negative symptoms and cognitive dysfunction in schizophrenia based on the NMDAR hypofunction hypothesis.

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Section: The Possible Reasons For Unsatisfactory Clinical Resultsmentioning

confidence: 99%

Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia

Huang

2021

Front. Neurosci.

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“…However, its use has decreased due to side effects, particularly addiction. Ketamine addiction is related to the interference of glutamate neurotransmission, which influences the establishment of the subcortical regions, such as nucleus accumbens, which is associated with addictive behaviours (18). Studies also show that there are specific antidepressant properties of glutamatergic medications targeting NMDA receptors (19,20) and effective reduction of suicidal ideation (5).…”

Section: Discussionmentioning

confidence: 99%

Severe Encephalatrophy and Related Disorders From Long-Term Ketamine Abuse: A Case Report and Literature Review

Lin-ying

Huang

Li³

et al. 2021

Front. Psychiatry

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Ketamine is a glutamate N-methyl D-aspartate receptor antagonist and an anaesthetic agent that has been effectively used to treat depression. However, ketamine has also been increasingly used for recreational purposes. The dissociative side-effects of ketamine use, such as hallucinations, are the reason for abuse. Additionally, long-term ketamine abuse has been highly associated with liver-gallbladder and urinary symptoms. The present study reports the case of a 28-year-old young male adult with an 8-year history of daily inhalation of ketamine. We investigated the association between ketamine abuse and the mechanism of its adverse effects, particularly encephalatrophy, and attempted to find a link between these disorders. These results would help us to better understand ketamine usage, ketamine abuse effects and the addictive mechanism. To the best of our knowledge, the present case is the first report of severe brain atrophy related to ketamine abuse. Details of the patient are presented and the mechanism of the encephalatropy-associated ketamine abuse is discussed. Furthermore, organ dysfunction following chronic ketamine abuse may indicate that the side effects are the result of comprehensive action on multiple regions in the brain.

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“…Non-invasive neuroimaging has contributed important insights into identifying the differences in brain structure and function between substance use disorders (SUD) patients and healthy individuals. Using structural magnetic resonance imaging (sMRI), researchers found that the brain structure of ketamine addicts had distinct changes, including significant atrophy of the frontal, parietal, or occipital cortex [ 98 , 119 ].…”

Section: Molecular Mechanism Of Non-opioid Anesthetic Drug Addictionmentioning

confidence: 99%

Non-Opioid Anesthetics Addiction: A Review of Current Situation and Mechanism

Deng,

Wu,

Gao

et al. 2023

Brain Sciences

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Drug addiction is one of the major worldwide health problems, which will have serious adverse consequences on human health and significantly burden the social economy and public health. Drug abuse is more common in anesthesiologists than in the general population because of their easier access to controlled substances. Although opioids have been generally considered the most commonly abused drugs among anesthesiologists and nurse anesthetists, the abuse of non-opioid anesthetics has been increasingly severe in recent years. The purpose of this review is to provide an overview of the clinical situation and potential molecular mechanisms of non-opioid anesthetics addiction. This review incorporates the clinical and biomolecular evidence supporting the abuse potential of non-opioid anesthetics and the foreseeable mechanism causing the non-opioid anesthetics addiction phenotypes, promoting a better understanding of its pathogenesis and helping to find effective preventive and curative strategies.

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Potential mechanisms for phencyclidine/ketamine-induced brain structural alterations and behavioral consequences

Cited by 9 publications

References 136 publications

Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia

Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia

Severe Encephalatrophy and Related Disorders From Long-Term Ketamine Abuse: A Case Report and Literature Review

Non-Opioid Anesthetics Addiction: A Review of Current Situation and Mechanism

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