Journal
PSYCHOPHARMACOLOGY
Volume 240, Issue 1, Pages 137-147Publisher
SPRINGER
DOI: 10.1007/s00213-022-06286-3
Keywords
Psilocybin; Fragile X syndrome; Rat; Novel object recognition; Microdoses
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The study aimed to test the effects of different doses of psilocybin on cognitive deficits in autism spectrum disorder (ASD) and fragile X syndrome (FXS). The results showed that systemic and oral administration of psilocybin microdoses normalized the aberrant cognitive performance in a rat model of FXS, suggesting the potential therapeutic effects of psilocybin in mitigating ASD-related cognitive deficits.
RationaleFragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neurodevelopmental disorders, manifesting as behavioral and emotional symptoms. Thus, compounds that stimulate serotonergic signaling such as psilocybin may offer promise as effective early interventions for developmental disorders such as ASD and FXS. ObjectivesThe aim of the present study was to test whether different protocols of psilocybin administration mitigate cognitive deficits displayed by the recently validated Fmr1-(& UDelta;)exon 8 rat model of ASD, which is also a model of FXS. ResultsOur results revealed that systemic and oral administration of psilocybin microdoses normalizes the aberrant cognitive performance displayed by adolescent Fmr1-(& UDelta;)exon 8 rats in the short-term version of the novel object recognition test-a measure of exploratory behavior, perception, and recognition. ConclusionsThese data support the hypothesis that serotonin-modulating drugs such as psilocybin may be useful to ameliorate ASD-related cognitive deficits. Overall, this study provides evidence of the beneficial effects of different schedules of psilocybin treatment in mitigating the short-term cognitive deficit observed in a rat model of FXS.
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