Role of the medial prefrontal cortex in the effects of rapid acting antidepressants on decision-making biases in rodents.


Journal

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907

Informations de publication

Date de publication:
12 2020
Historique:
received: 21 01 2020
accepted: 08 07 2020
revised: 01 07 2020
pubmed: 26 8 2020
medline: 24 6 2021
entrez: 26 8 2020
Statut: ppublish

Résumé

Major depressive disorder is a significant and costly cause of global disability. Until the discovery of the rapid acting antidepressant (RAAD) effects of ketamine, treatments were limited to drugs that have delayed clinical benefits. The mechanism of action of ketamine is currently unclear but one hypothesis is that it may involve neuropsychological effects mediated through modulation of affective biases (where cognitive processes such as learning and memory and decision-making are modified by emotional state). Previous work has shown that affective biases in a rodent decision-making task are differentially altered by ketamine, compared to conventional, delayed onset antidepressants. This study sought to further investigate these effects by comparing ketamine with other NMDA antagonists using this decision-making task. We also investigated the subtype selective GluN2B antagonist, CP-101,606 and muscarinic antagonist scopolamine which have both been shown to have RAAD effects. Both CP-101,606 and scopolamine induced similar positive biases in decision-making to ketamine, but the same effects were not seen with other NMDA antagonists. Using targeted medial prefrontal cortex (mPFC) infusions, these effects were localised to the mPFC. In contrast, the GABA

Identifiants

pubmed: 32842137
doi: 10.1038/s41386-020-00797-3
pii: 10.1038/s41386-020-00797-3
pmc: PMC7784869
doi:

Substances chimiques

Antidepressive Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2278-2288

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N015762/1
Pays : United Kingdom

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Auteurs

C A Hales (CA)

School of Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK.

J M Bartlett (JM)

School of Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK.

R Arban (R)

CNS Diseases Research, Boehringer Ingelheim GmbH & Co. KG, Biberach an der Riss, Germany.

B Hengerer (B)

CNS Diseases Research, Boehringer Ingelheim GmbH & Co. KG, Biberach an der Riss, Germany.

E S J Robinson (ESJ)

School of Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK. emma.s.j.robinson@bristol.ac.uk.

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