Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice
Lauri Elsilä, Elina Nagaeva, Jari-Pekka Luukkonen, Esa R. Korpi
bioRxiv Preprint Server December 12, 2024 preprint DOI: 10.1101/2024.12.12.628157 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory study |
|---|---|
| Population | C57Bl6/J mice |
| Interventions | LSD 25CN-NBOH |
| Topics | LSD Neuroplasticity Serotonin |
| Citations | 1 |
| Key points | LSD and 25CN-NBOH did not produce reliable place preference in mice, but LSD induced synaptic plasticity in medial VTA dopamine neurons. |
Abstract
The current research on psychedelic compounds such as lysergic amide diethylamide (LSD) is leaning heavily on the notion that psychedelics are not addictive. While much of the literature supports this argument, some of the common use patterns and the descriptions of the subjective effects of these compounds in humans, together with rather lacking and mixed data from non-human animal studies leave room for questions of potentially rewarding or reinforcing stimulus effects. Initiated by a surprising finding in a control study, we investigated these potential rewarding effects of LSD and a selective 5-HT2A agonist 25CN-NBOH using both unbiased and biased designs of conditioned place preference as well as ex vivo patch-clamp electrophysiology measurements of glutamatergic synaptic plasticity on midbrain ventral tegmental area (VTA) dopamine neurons in C57Bl6/J mice. Our results showed no reliable formation of place preference with either compound, agreeing with previous claims of psychedelics having at most weak reinforcing effects. However, we did observe single doses of the drugs, especially LSD, inducing synaptic plasticity in the medially located VTA dopamine neurons, implicating a role for the midbrain dopamine system in the effects of psychedelic drugs.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cites 24
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Phenomenology, Structure, and Dynamic of Psychedelic States Current Topics in Behavioral Neurosciences 2016
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology February 25, 2022
and 19 more in the library