Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.
Veronika Pohořalá, Martin Kuchař, Rainer Spanagel, Rick E Bernardi
Neuroscience November 1, 2024 DOI: 10.1016/j.neuroscience.2024.09.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Sample size | 82 |
| Population | Male and female mice and rats |
| Intervention | Psilocybin |
| Dose | 1.0 mg/kg (mice); 1.0 mg/kg or 2.5 mg/kg (rats) |
| Duration | 8-day self-administration and extinction (mice); 15-day self-administration and extinction (rats) |
| Topics | Addiction Psilocybin |
| Keywords | Addiction treatment Psychedelic research Substance abuse Cocaine dependence Animal studies Cocaine self-administration Mice Rats Reinstatement |
| Citations | 3 |
| Key findings | Psilocybin did not attenuate cue-induced reinstatement of cocaine-seeking in either mice or rats. |
Abstract
There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.
Comparable studies
Other preclinical and animal studies on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism | 2021 | Preclinical study | |
| Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse Male and female rats | 2020 | Preclinical animal study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Male and female Marchigian Sardinian alcohol-preferring (msP) rats | 2023 | Preclinical experimental study |
Citations in the library
Cites 13
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. The New England journal of medicine November 3, 2022
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action. The Journal of neuroscience : the official journal of the Society for Neuroscience November 8, 2023
- Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. Chinese medical journal December 20, 2023
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
and 8 more in the library