Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats.

This article investigates the acute and sustained antidepressant-like effects of psilocybin and D-lysergic acid diethylamide (LSD) in rats using the differential reinforcement of low-rate responding (DRL) 72-second schedule, a behavioral test with high predictive validity for antidepressant efficacy. The study found that acute administration of psilocybin (1 mg/kg) increased reinforced responses and response efficiency, indicating an immediate antidepressant-like effect, whereas LSD (0.08 mg/kg) showed no such effect. Neither compound demonstrated persistent antidepressant-like effects up to four weeks post-treatment. These findings suggest that while psilocybin may produce rapid antidepressant-like behavioral changes in non-stressed rats, detecting long-term efficacy in preclinical models like DRL 72s remains challenging and may require novel behavioral approaches.