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

This rodent study (2022) assessed the effects 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. Ketamine and psilocybin increased the levels of dopamine, serotonin, glutamate and GABA extracellular levels in the frontal cortex, while psilocybin also increased GABA in the reticular nucleus. Interestingly, no antidepressant -anxiety effects were observed.

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 were 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 behaviour 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). Behavioural 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 behaviour.”

Authors: Adam Wojtas, Agnieska Bysiek, Agnieska Wawrzczak-Bargiela, Zuanna Szych, Iwona Majcher-Maslanka, Monika Herian, Marzena Mackowiak & Krystyna Golembiowska

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Find this paper

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

https://doi.org/10.3390/ijms23126713

Open Access | Google Scholar | Backup | 🕊

Published in
International Journal of Molecular Sciences
June 16, 2022
0 citations

Study details

Topics studied
Depression Anxiety

Study characteristics
Animal Study Bio/Neuro

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