Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study
Adam Wojtas, Agnieszka Bysiek, Marzena Maćkowiak, Krystyna Gołembiowska, Agnieszka Wawrzczak-Bargieła
International Journal of Molecular Sciences December 20, 2023 DOI: 10.3390/ijms25010100 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Naive rats |
| Interventions | Psilocybin Ketamine |
| Topics | Psilocybin Esketamine Ketamine |
| Keywords | Limbic system Nucleus accumbens Amygdala Hippocampus Antidepressant Microdialysis Neurochemical Dopamine Pharmacology |
| Citations | 16 |
| Key points | Psilocybin and ketamine both increased dopamine and serotonin release in the nucleus accumbens and altered glutamate, GABA, and acetylcholine levels in limbic regions of rats, with psilocybin also producing anxiolytic effects. |
Abstract
The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin’s effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.
Comparable studies
Other preclinical and animal studies on psilocybin, 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 | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 14
- Psilocybin and the glutamatergic pathway: implications for the treatment of neuropsychiatric diseases. Pharmacological Reports December 1, 2024
- Molecular and Medical Aspects of Psychedelics International Journal of Molecular Sciences December 23, 2023
- The effect of low-dose psilocybin on brain neurotransmission and rat behavior. Progress in Neuro-Psychopharmacology and Biological Psychiatry April 2, 2025
- Classical psychedelics' action on brain monoaminergic systems. The international journal of biochemistry & cell biology November 1, 2024
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View. Molecular Neurobiology June 4, 2025
and 9 more in the library
Cites 28
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
and 23 more in the library