Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Lenka Seillier, Barbora Čechová, Alexandre Seillier et al.
3 citations
A single dose of psilocybin at 0.32 mg/kg, but not lower or higher doses, produced short- and long-term antidepressant-like effects in Wistar rats, as measured by the forced swim test, and also increased social interaction and sucrose preference. Higher doses of 1.0 and 3.2 mg/kg lacked antidepressant-like activity and instead reduced body temperature, locomotor activity, and weight gain. Brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex increased linearly with dose, dissociating from the inverted-U-shaped behavioral effects. The findings suggest a narrow therapeutic window for psilocybin, with the intermediate dose providing benefits without adverse effects seen at higher doses.
Journal of Psychopharmacology
June 23, 2026
Lenka Seillier, Alexandre Seillier, Morgan A. Zvolska et al.
Psilocybin produces rapid and sustained antidepressant-like effects in rats, as measured by reduced immobility and increased climbing in the forced swim test. Blocking the 5-HT2B receptor with the antagonist RS-127445 dose-dependently reversed these behavioral effects, indicating that 5-HT2B receptors are necessary for psilocybin's antidepressant-like activity. However, the same antagonist did not affect psilocybin-induced head-twitch responses, a proxy for psychedelic effects, suggesting that the antidepressant-like and psychedelic effects of psilocybin can be dissociated via different serotonin receptor subtypes.
Psychopharmacology
April 23, 2026
Stefani Kalli, Alina Davletova, Lenka Seillier et al.
Rats treated with phencyclidine (PCP) to model schizophrenia's negative symptoms showed reduced overall social interaction compared to controls, but the deficit was selective: some behaviors (e.g., Following) were impaired while others were not. A detailed analysis of 42 behaviors revealed that PCP-treated rats also displayed a persistent attentional bias toward the inanimate environment during both habituation and social exposure, suggesting their attention was displaced away from other rats. This multidimensional behavioral approach uncovers a more nuanced phenotype than simple total interaction time, indicating altered attentional allocation as a possible mechanism underlying social withdrawal in this model.
European Journal of Neuroscience
February 1, 2026
Aditya R. Kumar, Lenka Seillier, Martin Kuchař et al.
In a rat model of schizophrenia-like social withdrawal, an inhibitor of fatty acid amide hydrolase (FAAH) called URB597 reversed social deficits caused by the drug phencyclidine (PCP), but reduced social interaction in healthy control rats. The study measured CREB protein and its activated form pCREB across six cortical brain regions. Most regions showed little change, but the agranular insular cortex (AI) exhibited distinct effects: pCREB levels in the AI were reduced by both PCP and URB597 in controls, and pCREB in this region correlated positively with social interaction time. The findings identify the AI as a key brain area for social withdrawal and suggest that targeting the endocannabinoid system there may offer a therapeutic strategy for schizophrenia's negative symptoms.
PloS one
January 1, 2020
Alexandre Seillier, Alex A Martinez, Andrea Giuffrida
In a rat model of schizophrenia, low doses of THC (0.1 mg/kg) reversed social withdrawal and elevated anandamide levels caused by PCP, while higher doses (0.3, 1.0 mg/kg) worsened social deficits and disrupted dopamine neuron activity similarly to PCP alone. THC also activated the Akt/GSK3β pathway in a dose-dependent manner in both control and PCP-treated animals. These findings suggest that only low doses of THC may have beneficial effects on behavioral, neurochemical, and electrophysiological correlates of schizophrenia symptoms, potentially informing the debate on marijuana use as self-medication in patients.