Rapid antidepressant-like effect of non-hallucinogenic psychedelic analog lisuride, but not hallucinogenic psychedelic DOI, in lipopolysaccharide-treated mice
Youge Qu, Lijia Chang, Li Ma, Xiayun Wan, Kenji Hashimoto
Pharmacology, Biochemistry, and Behavior December 5, 2022 DOI: 10.1016/j.pbb.2022.173500 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal study Peer reviewed |
|---|---|
| Population | Lipopolysaccharide (LPS)-treated mice |
| Interventions | DOI lisuride (R)-ketamine |
| Dose | DOI 2.0 mg/kg, lisuride 1.0 mg/kg, (R)-ketamine 10 mg/kg |
| Duration | 23 hours after LPS administration |
| Topics | Ketamine Serotonin |
| Keywords | Lisuride Hallucinogen Pharmacology Antidepressant Hippocampus Agonist Receptor |
| Citations | 42 |
| Key points | Lisuride and (R)-ketamine, but not DOI, ameliorated depression-like behavior and decreased dendritic spine density in LPS-treated mice, suggesting 5-HT2AR may not be central to rapid antidepressant actions of psychedelics. |
Abstract
Classical psychedelics with 5-hydroxytryptamine-2A receptor (5-HT2AR) agonism have rapid antidepressant actions in patients with depression. However, there is an ongoing debate over the role of 5-HT2AR in the antidepressant-like actions of psychedelics. In this study, we compared the 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 agonisms), and the novel antidepressant (R)-ketamine on depression-like behavior and the decreased dendritic spine density in the brain of lipopolysaccharide (LPS)-treated mice. Saline (10 ml/kg), DOI (2.0 mg/kg), lisuride (1.0 mg/kg), or (R)-ketamine (10 mg/kg) was administered intraperitoneally to LPS (0.5 mg/kg, 23 h before)-treated mice. Both lisuride and (R)-ketamine significantly ameliorated the increased immobility time of forced swimming test, and the decreased dendritic spine density in the prelimbic region of medial prefrontal cortex, CA3 and dentate gyrus of hippocampus of LPS-treated mice. In contrast, DOI did not improve these changes produced after LPS administration. This study suggests that antidepressant-like effect of lisuride in LPS-treated mice is not associated with 5-HT2AR-related psychedelic effects. It is, therefore, unlikely that 5-HT2AR may play a major role in rapid-acting antidepressant actions of psychedelics although further detailed study is needed.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 35
- Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action. Journal of Neuroscience November 8, 2023
- Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player? Neuropsychopharmacology March 1, 2024
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews November 30, 2023
and 30 more in the library
Cites 39
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- 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
and 34 more in the library