In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept

Rodríguez, Carolyn I.; Kegeles, Lawrence S.; Levinson, Amanda; Ogden, R. Todd; Mao, Xiangling; Milak, Matthew S.; Vermes, Donna; Xie, Shan; Hunter, Liane E.; Flood, Pamela; Moore, Holly; Shungu, Dikoma C.; Simpson, Helen Blair

doi:10.1016/j.pscychresns.2015.06.001

Cited by 51 publications

(50 citation statements)

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“…Gonadal hormones, such as estrogen and progesterone, may also potentiate the rapidity and potency of ketamine’s antidepressant effects, as demonstrated in preclinical models (Carrier and Kabbaj, 2013; Franceschelli et al, 2015; Hashimoto, 2016). Lastly, ketamine interaction with GABA receptors has been implicated in various clinical pathologies, including obsessive-compulsive disorder (Rodriguez et al, 2015), depression (Perrine et al, 2014) and learning disabilities following chronic exposure (Tan et al, 2011). …”

Section: Proposed Mechanisms Of Actionsmentioning

confidence: 99%

Ketamine: 50 Years of Modulating the Mind

Vlisides

2016

Front. Hum. Neurosci.

282

212

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Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine’s effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal (“top down”) distribution. This proposed mechanism of general anesthesia has since been demonstrated with anesthetics in other pharmacological classes as well. Ketamine remains invaluable to the fields of anesthesiology and critical care medicine, in large part due to its ability to maintain cardiorespiratory stability while providing effective sedation and analgesia. Furthermore, there may be an emerging role for ketamine in treatment of refractory depression and Post-Traumatic Stress Disorder. In this article, we review the history of ketamine, its pharmacology, putative mechanisms of action and current clinical applications.

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Section: Proposed Mechanisms Of Actionsmentioning

confidence: 99%

Ketamine: 50 Years of Modulating the Mind

Vlisides

2016

Front. Hum. Neurosci.

282

212

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“…Previous studies suggest that ketamine increases glutamatergic transmission and alters excitatory/inhibitory balance within the mPFC 45,46,47 . However, our baseline photometry recordings ( Figure 1) indicated that KO animals had increased fronto-striatal activity compared to WT animals during grooming, leading us to hypothesize that the therapeutic effect of ketamine might be associated with decreasing activity in this projection to resemble WT activity patterns during grooming.…”

Section: Ketamine Selectively Increases In Vivo Fronto-striatal Projementioning

confidence: 98%

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior

Davis

Minerva

Lario

et al. 2020

Preprint

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AbstractObsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fastacting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine’s therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity rescued compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine’s therapeutic effects in OCD.

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“…Ketamine (Ketalar), a voltage-dependent, non-competitive and non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, acts by inhibiting the fluidity of calcium and sodium cations in the presence of glutamate and glycine (Niciu, Henter, Luckenbaugh, Zarate, Jr., & Charney, 2014). In adults with OCD, ketamine infusions appear to normalize low GABA levels in medial prefrontal cortex (Rodriguez et al, 2015). While ketamine has shown utility in the treatment of refractory depression (Iadarola et al, 2015), only case reports are available for the use of ketamine in OCD.…”

Section: Psychopharmacologymentioning

confidence: 99%

Pediatric Obsessive-Compulsive Disorder: A Psychopharmacology Update

Grados¹,

Torrico²,

Frederick³

et al. 2016

Child and Adolescent Psychopharmacology News

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This publication is intended to provide accurate and authoritative information regarding the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering medical, psychological, financial, legal, or other professional services. The recommended doses of medications cited in this newsletter are not meant to serve as a guide for prescribing of medications. Physicians, please check the manufacturer's product information sheet or the PHYSICIAN'S DESK REFERENCE for further information and contraindications. 1 • CAPN 21(1) Educational Objectives Upon completion of this activity, participants should be able to: • Evaluate treatment approaches to pediatric OCD. • Review traditional medications useful in treating pediatric OCD with comorbidity and for specific subtypes, such as tic-related OCD. Target Audience This CME activity is intended for child and adult psychiatrists, pediatricians and other healthcare professionals with an interest in the psychopharmacology and treatment practices for child and adolescent psychiatric disorders.

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In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept

Cited by 51 publications

References 53 publications

Ketamine: 50 Years of Modulating the Mind

Ketamine: 50 Years of Modulating the Mind

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior

Pediatric Obsessive-Compulsive Disorder: A Psychopharmacology Update

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