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Modulation of thala...
Modulation of thalamo-cortical activity by the NMDA receptor antagonists ketamine and phencyclidine in the awake freely-moving rat
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- Amat-Foraster, Maria (author)
- H. Lundbeck A/S,University of Copenhagen,CSIC Institute of Biomedical Research of Barcelona (IIBB),Institutd' Investigacions Biomèdiques August Pi iSunyer (IDIBAPS)
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- Celada, Pau (author)
- CSIC Institute of Biomedical Research of Barcelona (IIBB),CIBER Salud Mental (CIBERSAM),Institutd' Investigacions Biomèdiques August Pi iSunyer (IDIBAPS)
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- Richter, Ulrike (author)
- Lund University,Lunds universitet,Integrativ neurofysiologi,Forskargrupper vid Lunds universitet,Neuronano Research Center (NRC),Integrative Neurophysiology,Lund University Research Groups,H. Lundbeck A/S
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- Jensen, Anders A. (author)
- University of Copenhagen
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- Plath, Niels (author)
- H. Lundbeck A/S
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- Artigas, Francesc (author)
- Institutd' Investigacions Biomèdiques August Pi iSunyer (IDIBAPS),CSIC Institute of Biomedical Research of Barcelona (IIBB),CIBER Salud Mental (CIBERSAM)
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- Herrik, Kjartan F. (author)
- H. Lundbeck A/S
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H Lundbeck A/S University of Copenhagen (creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 158
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Abstract
Subject headings
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- Non-competitive N-methyl-D-aspartate receptor antagonists mimic schizophrenia symptoms and produce immediate and persistent antidepressant effects. We investigated the effects of ketamine and phencyclidine (PCP) on thalamo-cortical network activity in awake, freely-moving male Wistar rats to gain new insight into the neuronal populations and brain circuits involved in the effects of NMDA-R antagonists. Single unit and local field potential (LFP) recordings were conducted in mediodorsal/centromedial thalamus and in medial prefrontal cortex (mPFC) using microelectrode arrays. Ketamine and PCP moderately increased the discharge rates of principal neurons in both areas while not attenuating the discharge of mPFC GABAergic interneurons. They also strongly affected LFP activity, reducing beta power and increasing that of gamma and high-frequency oscillation bands. These effects were short-lasting following the rapid pharmacokinetic profile of the drugs, and consequently were not present at 24 h after ketamine administration. The temporal profile of both drugs was remarkably different, with ketamine effects peaking earlier than PCP effects. Although this study is compatible with the glutamate hypothesis for fast-acting antidepressant action, it does not support a local disinhibition mechanism as the source for the increased pyramidal neuron activity in mPFC. The short-lasting increase in thalamo-cortical activity is likely associated with the rapid psychotomimetic action of both agents but could also be part of a cascade of events ultimately leading to the persistent antidepressant effects of ketamine. Changes in spectral contents of high-frequency bands by the drugs show potential as translational biomarkers for target engagement of NMDA-R modulators.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Ketamine
- Neuronal oscillations
- NMDA receptor antagonists
- Phencyclidine
- Single unit recordings
- Thalamo-cortical networks
Publication and Content Type
- art (subject category)
- ref (subject category)
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