The effect of Psilocybe cubensis alkaloids on depressive-like behavior in mice exposed to maternal separation with respect to hippocampal gene expression and DNA methylation of Slc6a4 and Nr3c1

Feb 19, 2025Behavioural pharmacology

Psilocybe cubensis compounds and their link to depression-like behavior, brain gene activity, and gene regulation in mice separated from their mothers

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Abstract

Maternal separation significantly induced depressive-like behavior and anxiety-like behavior in mice.

Maternal separation decreased locomotor activity in mice.
Both Slc6a4 and Nr3c1 gene expression were reduced following maternal separation.
Maternal separation increased the methylation level of Slc6a4 and Nr3c1 in the hippocampus.
P. cubensis extract significantly reversed the behavioral effects induced by maternal separation.
P. cubensis may influence serotonergic signaling by altering the expression and methylation of Slc6a4 in the hippocampus.

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Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis extract (PCE) on depressive-like and anxiety-like behaviors, and locomotor activity in mice exposed to early maternal separation. Also, we assessed the expression and methylation level of Slc6a4 and Nr3c1 in the hippocampus. Maternal separation was done in postnatal days (PNDs) 2-18. PCE was intraperitoneally injected at the dose of 20 mg/kg at PND 60, and our tests were done at days 1, 3, and 10, of administration. The results showed that maternal separation significantly induced depressive-like behavior in the forced swim test and anxiety-like behavior in the open field test (OFT). Also, maternal separation decreased locomotor activity in the OFT. In addition, maternal separation decreased the expression and increased the methylation level of both Slc6a4 and Nr3c1 in the hippocampus. However, PCE significantly reversed all these effects. In conclusion, it seems that P. cubensis affects serotonergic signaling via altering Slc6a4 expression and methylation level in the hippocampus of mice. The effect of P. cubensis on Nr3c1 expression and methylation level may also lead to alter the function of the hypothalamus-pituitary-adrenal axis and the stress response in mice exposed to maternal separation.

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The effect of Psilocybe cubensis alkaloids on depressive-like behavior in mice exposed to maternal separation with respect to hippocampal gene expression and DNA methylation of Slc6a4 and Nr3c1

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