Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning
Briony J. Catlow, Shijie Song, Daniel Paredes, Cheryl L. Kirstein, Juan Sanchez‐ramos
Experimental Brain Research June 1, 2013 DOI: 10.1007/s00221-013-3579-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Psilocybin 25I-NBMeO ketanserin |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Fear conditioning Dentate gyrus Hippocampal formation Extinction optical mineralogy Classical conditioning Amygdala Hippocampus |
| Citations | 266 |
| Key findings | Low doses of psilocybin facilitate extinction of conditioned fear responses in mice, an effect not mediated by decreased hippocampal neurogenesis. |
Abstract
Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.
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 | |
| 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 | |
| Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice | 2021 | Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice |
Citations in the library
Cited by 202
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- 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
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
- LSD-induced entropic brain activity predicts subsequent personality change. Human Brain Mapping May 6, 2016
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
and 197 more in the library
Cites 11
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- The pharmacology of psilocybin Addiction Biology October 1, 2002
and 6 more in the library