Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.
Claire A Hales, Conor J Houghton, Emma Robinson
European Neuropsychopharmacology December 2017 DOI: 10.1016/j.euroneuro.2017.09.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preprint Peer reviewed |
|---|---|
| Population | Rodents |
| Topics | Ketamine |
| Keywords | Antidepressants Behaviour Diffusion model Judgement bias Rodent |
| Key points | Positive judgement biases were induced over timeframes mirroring the rapid versus delayed antidepressant efficacy seen in patients. Diffusion modelling indicated the antidepressants tested have different effects on decision making processes, suggesting they may act through different neurobiological substrates. The authors propose this behaviour-plus-modelling approach may help investigate rapid antidepressant mechanisms and assess new treatments. |
Abstract
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients would be reflected in affective biases and decision making behaviour in rodents. The diffusion model was also used to investigate the underlying decision making processes. Positive biases were induced in this task over timeframes that mirror the rapid versus delayed antidepressant efficacy of the drugs in clinical populations. Diffusion modelling revealed that the antidepressants tested also have different effects on decision making processes, suggesting they may act through different neurobiological substrates. This combination of behaviour and computational modelling may provide a useful approach to further investigate the mechanisms underlying rapid antidepressant effect and assess potential new treatments.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Preclinical models for evaluating psychedelics in the treatment of major depressive disorder. British Journal of Pharmacology October 28, 2024
- Cognitive and affective models of psychedelics in rodents. International review of neurobiology 2025
- Role of the medial prefrontal cortex in the effects of rapid acting antidepressants on decision-making biases in rodents bioRxiv (Cold Spring Harbor Laboratory) January 23, 2020
- A continuum hypothesis of psychotomimetic rapid antidepressants. Brain and Neuroscience Advances 2021
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy Neuropsychopharmacology March 5, 2015
and 2 more in the library