Prophylactic effects of arketamine, but not hallucinogenic psychedelic DOI nor non-hallucinogenic psychedelic analog lisuride, in lipopolysaccharide-treated mice and mice exposed to chronic restrain stress.
Guilin Liu, Li Ma, Youge Qu, Xiayun Wan, Dan Xu, Mingming Zhao, Rumi Murayama, Kenji Hashimoto
Pharmacology, Biochemistry, and Behavior December 1, 2023 DOI: 10.1016/j.pbb.2023.173659 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Male mice |
| Interventions | DOI lisuride arketamine |
| Dose | DOI 2.0 or 4.0 mg/kg, lisuride 1.0 or 2.0 mg/kg, arketamine 10 mg/kg |
| Duration | Pretreatment 6 days before LPS challenge or 1 day before 7-day chronic restraint stress |
| Topics | Ketamine |
| Keywords | Chronic stress Inflammation Prophylactic Psychedelic |
| Citations | 16 |
| Key points | Arketamine, but not DOI or lisuride, showed long-lasting prophylactic effects against depression-like behaviors in LPS-treated and chronically stressed male mice. |
Abstract
Anesthetic ketamine and classical psychedelics that act as 5-hydroxytryptamine-2A receptor (5-HT2AR) agonists demonstrated rapid and sustained antidepressant actions in patients with treatment-resistant depression. The new antidepressant arketamine is reported to cause long-lasting prophylactic effects in lipopolysaccharide (LPS)-treated mice and mice exposed to chronic restrain stress (CRS). However, no study has compared the prophylactic effects of DOI (2,5-dimethoxy-4-iodoamphetamine: a hallucinogenic psychedelic drug with potent 5-HT2AR agonism), lisuride (non-hallucinogenic psychedelic analog with 5-HT2AR and 5-HT1AR agonism), and arketamine on depression-like behaviors in mice. Saline (10 ml/kg), DOI (2.0 or 4.0 mg/kg), lisuride (1.0 or 2.0 mg/kg), or arketamine (10 mg/kg) was administered intraperitoneally (i.p.) to male mice 6 days before administration of LPS (1.0 mg/kg). Pretreatment with aketamine, but not DOI and lisuride, significantly ameliorated body weight loss, splenomegaly, the increased immobility time of forced swimming test (FST), and the decreased expression of PSD-95 in the prefrontal cortex (PFC) of LPS-treated mice. In another test, male mice received the same treatment one day before CRS (7 days). Pretreatment with aketamine, but not DOI and lisuride, significantly ameliorated the increased FST immobility time, the reduced sucrose preference in the sucrose preference test, and the decreased expression of PSD-95 in the PFC of CRS-exposed mice. These findings suggest that, unlike to arketamine, both DOI and lisuride did not exhibit long-lasting prophylactic effects in mouse models of depression.
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 13
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress. Neurobiology of Disease December 1, 2023
- Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis. Neurobiology of Disease September 1, 2024
- Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1. Journal of Affective Disorders December 15, 2024
and 8 more in the library
Cites 34
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 29 more in the library