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Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Adam Wojtas, Agnieszka Bysiek, Agnieszka Wawrzczak-Bargieła, Zuzanna Szych, Iwona Majcher‐maślanka, Monika Herian, Marzena Maćkowiak, Krystyna Gołembiowska

International Journal of Molecular Sciences June 16, 2022 DOI: 10.3390/ijms23126713 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions Ketamine Psilocybin
Dose 10 mg/kg ketamine; 2 and 10 mg/kg psilocybin
Duration Single administration; behavioral tests conducted 24 h after drug administration
Topics Psilocybin Esketamine Ketamine
Keywords Pharmacology Nmda receptor Glutamate receptor
Citations 110
Key findings Ketamine and psilocybin alter neurotransmitter levels and cause oxidative DNA damage in rats, but show no antidepressant or anxiolytic effects in behavioral tests 24 hours after administration.

Abstract

Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex and reticular nucleus of the thalamus using microdialysis. The genotoxic effect and density of glutamate receptor proteins was measured with comet assay and Western blot, respectively. An open field test, light–dark box test and forced swim test were conducted to examine rat behavior 24 h after drug administration. Ketamine (10 mg/kg) and psilocybin (2 and 10 mg/kg) increased dopamine, serotonin, glutamate and GABA extracellular levels in the frontal cortex, while psilocybin also increased GABA in the reticular nucleus of the thalamus. Oxidative DNA damage due to psilocybin was observed in the frontal cortex and from both drugs in the hippocampus. NR2A subunit levels were increased after psilocybin (10 mg/kg). Behavioral tests showed no antidepressant or anxiolytic effects, and only ketamine suppressed rat locomotor activity. The observed changes in neurotransmission might lead to genotoxicity and increased NR2A levels, while not markedly affecting animal behavior.

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

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Psilocybin Esketamine Ketamine Serotonin