ORALLY ADMINISTERED PSILOCYBIN DOSE-DEPENDENTLY DISTORTS VISUAL PERCEPTION IN MALE RATS

Psychedelic agents such as psilocybin represent a promising emerging treatment class for conditions such as treatment-resistant depression and post-traumatic stress disorder. Evidence suggests that treatment efficacy may correlate with the individual’s subjective sensitivity to psychedelic effects; therefore, understanding the mechanisms underlying these effects through preclinical work is essential. To model the distortions in visual perception reported by human subjects, we optimised a male rat two-choice visual discrimination touchscreen task. We used static vertical striped stimuli (correct) versus horizontal (control) or wavy stimuli of varying difficulty (test), providing a high-throughput method to test the effect of orally administered psilocybin (COMP360 psilocybin, Compass Pathways’ investigational proprietary formulation of synthetic psilocybin). Moderate or high psilocybin doses significantly decreased accuracy (FDose(1.93, 32.88)=7.24, p = 0.003, 𝜂_p² = 0.30; 1mg/kg: t(32.88) = 3.54, p=0.0076; 3mg/kg: t(32.88) = 3.08, p=0.0026, versus Vehicle, RM ANOVA) and increased response latency (FDose(1.92, 32.68) = 94.29, p < 0.001, 𝜂_p²= 0.85; 1mg/kg: t(17) = 4.38, p=0.0011; 3mg/kg: t(17) = 13.05 p<0.0001, RM ANOVA), indicating impaired task performance. A low dose (0.3mg/kg) did not elicit similar effects, establishing a dose-dependent effect of psilocybin on visual discrimination in rats.
Currently, we are exploring the relationship between the dose effects in the visual modality and the reported beneficial effects of psilocybin on enhancing Pavlovian fear extinction – a rodent analogue of exposure therapy. This study provides a foundation for exploring the neural mechanisms underlying psilocybin-induced perceptual changes, which may parallel the visual distortions seen in humans experiencing the psychedelic effects of psilocybin.