Psilocybin shows pronounced antidepressant and pro-social effects in both Wistar-Kyoto rats, which model treatment-resistant depression, and normal Wistar rats, but with distinct time courses. The study found behavioral differences between the strains, including passive behavior and social withdrawal in Wistar-Kyoto rats. Psilocybin modulated brain-derived neurotrophic factor signaling differently in each strain and altered activity-regulated cytoskeleton-associated protein expression specifically in Wistar-Kyoto rats. These strain-specific neuroplasticity changes offer insights into the mechanisms behind psilocybin's efficacy in treatment-resistant depression.
Treatment-resistant depression (TRD) is a subset of major depressive disorder where standard antidepressants fail. No universal criteria exist for TRD, but it commonly involves non-response to at least two medication trials. Up to 60% of TRD patients may be pseudo-TRD, where factors like gender, age, and hormonal disturbances contribute to drug resistance. The complexity of TRD makes diagnosis and treatment challenging. This review discusses animal models that meet validity criteria for TRD, including chronic mild stress and the Wistar Kyoto rat strain. It also examines preclinical studies of novel therapies such as ketamine, deep brain stimulation, and psychedelic drugs.