Agonist E-6837 and antagonist SB-271046 of 5-HT6 receptors both reverse the depressive-like effect induced in mice by subchronic ketamine administration
José E. Suárez-Santiago, Alfredo Briones-Aranda, Judith Espinosa-Raya, Ofir Picazo
Behavioural Pharmacology October 1, 2017 DOI: 10.1097/fbp.0000000000000327 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine E-6837 SB-271046 |
| Dose | Ketamine 10 mg/kg/day; E-6837 10 and 20 mg/kg; SB-271046 10 mg/kg |
| Duration | 5 days of ketamine administration |
| Measures | Forced-swimming test, tail-suspension test |
| Topics | Esketamine Ketamine |
| Key points | The 5-HT6 receptor agonist E-6837 (10 and 20 mg/kg) and the antagonist SB-271046 (10 mg/kg) each reduced ketamine-induced immobility in mice, suggesting these ligands may modulate mood. The authors note that the physiological mechanisms require further study. |
Abstract
Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-d-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal). Repeated ketamine administration alone increased the immobility time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and 20 mg/kg caused a significant reduction of immobility in the tail-suspension test and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also elicited an antidepressant-like effect in both tests. The current findings suggest an important role for these 5-HT6R ligands as mood modulators. However, it is necessary to explore the physiological mechanisms involved in this process in greater detail.
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
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One? Frontiers in Psychiatry May 11, 2021
- The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine Behavioural Pharmacology June 1, 2022
- Stress-sensitive antidepressant-like effects of ketamine in the mouse forced swim test PLoS One April 15, 2019
Cites 4
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice. Behavioural Brain Research October 1, 2016
- Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans Frontiers in Pharmacology September 27, 2016
- Mouse strain differences in phencyclidine-induced behavioural changes. The International Journal of Neuropsychopharmacology July 1, 2012