Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice.
Paul J Fletcher, Zhaoxia Li, Xiao Dong Ji, Anh D Lê
Pharmacology, Biochemistry, and Behavior February 1, 2024 DOI: 10.1016/j.pbb.2023.173703 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male DBA/2J mice |
| Interventions | Psilocybin TCB-2 |
| Dose | psilocybin 0.3 and 1 mg/kg; TCB-2 1 and 3 mg/kg |
| Duration | 5 consecutive days of treatment, followed by a challenge test with 15-minute activity measurement |
| Topics | Psilocybin Serotonin |
| Keywords | Ethanol Locomotor activity Sensitization Tcb-2 Addiction research Alcohol studies Drug interactions Psychedelics Behavioral neuroscience |
| Citations | 2 |
| Key findings | Psilocybin and TCB-2 at behaviorally effective doses did not reverse the sensitization of ethanol-induced locomotor activity in mice. |
Abstract
Psychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in AUD may involve an action to reverse or offset effects of long-term changes induced by EtOH. This possibility was examined by investigating whether psilocybin, or the 5-HT2A receptor agonist TCB-2, counteracted established sensitization of EtOH-induced locomotor activity. Male DBA/2J mice received repeated injections of 2.2 g/kg EtOH to induce a sensitized locomotor activity response. In two experiments separate groups of mice were then injected with psilocybin (0, 0.3 and 1 kg/kg) or TCB-2 (0, 1 and 3 mg/kg) on 5 consecutive days. Next, mice were challenged with 1.8 g/kg EtOH and locomotor activity measured for 15 min. Relative to naïve controls, previously sensitized mice showed enhanced locomotor activity to the challenge dose. Despite reducing locomotor activity in their own right psilocybin and TCB-2 did not alter the strength of this sensitized response. Psilocybin and TCB-2 at behaviourally effective doses did not reverse sensitization of EtOH-induced activity. This suggests that mechanisms involved in mediating short-term reductions in EtOH intake by psilocybin or TCB-2 may not involve a capacity of these drugs to offset enduring changes in behaviour and any underlying neural adaptations induced by repeated intermittent exposure to EtOH.
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
Cites 30
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Cessation and reduction in alcohol consumption and misuse after psychedelic use Journal of Psychopharmacology May 14, 2019
and 25 more in the library