The effect of ((−)-2-oxa-4-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), an mGlu2/3 receptor agonist, on EEG power spectra and coherence in ketamine model of psychosis

Fujáková, M.; Páleníček, Tomáš; Brunovský, Martin; Gorman, Ingmar; Tylš, Filip; Kubešová, Anna; Řı́pová, Daniela; Krajča, Vladimı́r; Horáček, Jiří

doi:10.1016/j.pbb.2014.03.001

Cited by 15 publications

(14 citation statements)

References 53 publications

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“…This effect was thought to be due to the antipsychotic actions of mGlu 2/3 receptor activation, since this pharmacological manipulation can prevent excessive glutamate levels in the prefrontal cortex of rodents after administration of NMDAR antagonists, which causes schizophrenia endophenotypes (59,101,102). Nevertheless, activation of mGlu 2/3 receptors using the same doses as the ones used to prevent ketamine-induced gamma qEEG oscillations did not prevent ketamine-associated disruption in sensorimotor gating assessed via the prepulse inhibition task in rodents (66,103,104). These findings highlight that the actions of mGlu 2/3 activation to reduce ketamine-induced increase in gamma power are unlikely to represent prevention of NMDAR inhibition-mediated psychotomimetic actions.…”

Section: Discussionmentioning

confidence: 99%

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions

Zanos

Highland

Stewart

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

114

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Currently approved antidepressant drugs often take months to take full effect, and ∼30% of depressed patients remain treatment resistant. In contrast, ketamine, when administered as a single subanesthetic dose, exerts rapid and sustained antidepressant actions. Preclinical studies indicate that the ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a rapid-acting antidepressant drug candidate with limited dissociation properties and abuse potential. We assessed the role of group II metabotropic glutamate receptor subtypes 2 (mGlu 2 ) and 3 (mGlu 3 ) in the antidepressant-relevant actions of (2R,6R)-HNK using behavioral, genetic, and pharmacological approaches as well as cortical quantitative EEG (qEEG) measurements in mice. Both ketamine and (2R,6R)-HNK prevented mGlu 2/3 receptor agonist (LY379268)induced body temperature increases in mice lacking the Grm3, but not Grm2, gene. This action was not replicated by NMDA receptor antagonists or a chemical variant of ketamine that limits metabolism to (2R,6R)-HNK. The antidepressant-relevant behavioral effects and 30-to 80-Hz qEEG oscillation (gamma-range) increases resultant from (2R,6R)-HNK administration were prevented by pretreatment with an mGlu 2/3 receptor agonist and absent in mice lacking the Grm2, but not Grm3 −/− , gene. Combined subeffective doses of the mGlu 2/3 receptor antagonist LY341495 and (2R,6R)-HNK exerted synergistic increases on gamma oscillations and antidepressant-relevant behavioral actions. These findings highlight that (2R,6R)-HNK exerts antidepressant-relevant actions via a mechanism converging with mGlu 2 receptor signaling and suggest enhanced cortical gamma oscillations as a marker of target engagement relevant to antidepressant efficacy. Moreover, these results support the use of (2R,6R)-HNK and inhibitors of mGlu 2 receptor function in clinical trials for treatment-resistant depression either alone or in combination. ketamine | hydroxynorketamine | antidepressant | mGlu 2 receptor |

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Section: Discussionmentioning

confidence: 99%

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions

Zanos

Highland

Stewart

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

114

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“…In a similar vein, the positive allosteric modulator TASP0433864 or orthosteric agonist at the metabotropic receptor 2 LY379268 completely reversed the ketamine-induced power increase in high-frequency bands [71,81,82] and partially reversed disrupted coherence [83]. …”

Section: P-eeg In Modeled Animalsmentioning

confidence: 99%

Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications

Drinkenburg

Ruigt²,

Ahnaou

2015

Neuropsychobiology

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The contemporary value of animal pharmaco-electroencephalography (p-EEG)-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. While p-EEG in humans and animals has been shown to be closely related in terms of underlying neuronal substrates, both translational and back-translational approaches are being used to address extrapolation issues and optimize the translational validity of preclinical animal p-EEG paradigms and data. Present applications build further on animal p-EEG and pharmaco-sleep EEG findings, but also on stimulation protocols, more specifically pharmaco-event-related potentials. Pharmaceutical research into novel treatments for neurological and psychiatric diseases has employed an increasing number of pharmacological as well as transgenic models to assess the potential therapeutic involvement of different neurochemical systems and novel drug targets as well as underlying neuronal connectivity and synaptic function. Consequently, p-EEG studies, now also readily applied in modeled animals, continue to have an important role in drug discovery and development, with progressively more emphasis on its potential as a central readout for target engagement and as a (translational) functional marker of neuronal circuit processes underlying normal and pathological brain functioning. In a similar vein as was done for human p-EEG studies, the contribution of animal p-EEG studies can further benefit by adherence to guidelines for methodological standardization, which are presently under construction by the International Pharmaco-EEG Society (IPEG).

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“…The EEG was recorded using a BrainScope system 7 days after the implantation of the electrodes. Methods of electrode implantation and recording were in detaile described in [2], [3]. All the experiments respected the Guidelines of the European Union (86/609/EU) and followed the instructions of the National Committee for the Care and Use of Laboratory Animals.…”

Section: Datamentioning

confidence: 99%

“…All points are moved in the coordinate system centered at the center of the sphere (x 0 , y 0 , z 0 ), see (2). Than we compute length of this vector: |POS|, see (3). We scale the vector by using length of ideal radius of the sphere and we get a new vector Q POS , see (4).…”

Section: Projection On Spherementioning

confidence: 99%

“…Different number of electrodes and differ-ent electrode location are used in animal studies. For example 12 electrodes was implanted in the study of Palenicek et al [2] and Fujakova et al [3], 7 electrodes were implanted in the study of Cavelli et al [4], 2-4 electrodes were implanted in the study of Cambiaghi et al [5] and 32 electrodes were implanted in the study of Bae et al [6].…”

Section: Introductionmentioning

confidence: 99%

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Methods for Animal Brain Mapping

Tylš¹,

Krajča²,

Páleníček³

et al. 2018

RADIOENGINEERING

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Measurements of brain electrical activity in animals are essential for the validation of the pharmaco-effect of drugs. The way to evaluate these recordings should be comparable to that of EEG in humans. Methods that visualize the results of the measured EEG recording include brain mapping in two-dimensional or three-dimensional space. The most commonly used methods of interpolation techniques in humans are spherical splines and 3D splines. We measured nine brains of Wistar rats and compared them with a brain model from the atlas (Brain Atlas Reconstructor, BAR). We validated the brain model of Wistar rat for future use. We implemented a module in MATLAB 2015a for brain mapping, specifically, we implemented algorithms for spherical and 3D spline mapping. The root mean square error of the spherical spline method is 0.5943 in the case of testing signal and 0.6291/0.6388 in the case of real data estimation. The root mean square error of the 3D spline method is 0.4334 in the case of testing signal and 0.0849/0.0768 in the case of real data estimation. Our results show that the 3D spline method with the projection on sphere gives significantly better 3D potential map than spherical splines.

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The effect of ((−)-2-oxa-4-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), an mGlu2/3 receptor agonist, on EEG power spectra and coherence in ketamine model of psychosis

Cited by 15 publications

References 53 publications

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions

Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications

Methods for Animal Brain Mapping

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The effect of ((−)-2-oxa-4-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), an mGlu2/3 receptor agonist, on EEG power spectra and coherence in ketamine model of psychosis

Cited by 15 publications

References 53 publications

( 2R,6R )-hydroxynorketamine exerts mGlu 2 receptor-dependent antidepressant actions

( 2R,6R )-hydroxynorketamine exerts mGlu 2 receptor-dependent antidepressant actions

Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications

Methods for Animal Brain Mapping

Contact Info

Product

Resources

About

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions

( 2R,6R )-hydroxynorketamine exerts mGlu ₂ receptor-dependent antidepressant actions