Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats
Journal of Psychopharmacology – October 16, 2023
Source: OpenAlex
Summary
Psilocybin, an alkaloid hallucinogen, delivered an immediate antidepressant-like effect in rats, a key finding for medicine. Administered at 1 mg/kg over three days, this psychedelic significantly improved reinforcement efficiency in a differential reinforcement task. However, neither psilocybin nor LSD (0.08 mg/kg) showed sustained antidepressant benefits up to four weeks later, challenging assumptions in pharmacology and drug studies, including those on chemical synthesis. This psychology experiment illuminates the complex neurotransmitter receptor influence on behavior.
Abstract
Background: In clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports on psychedelics’ effects most often address their acute actions, and different tests and models provide inconsistent results. The goal of this study was to examine whether the treatment with psilocybin and/or LSD would demonstrate immediate and/or sustained antidepressant-like effects in the differential reinforcement of low-rate responding (DRL) schedule in rats. In contrast to the antidepressant screening tools, the DRL 72s test is known to detect antidepressants with high predictive validity as it differentiates clinically effective antidepressants from other psychoactive drugs in non-stressed animals. Methods: Adult male Sprague Dawley rats were injected over three consecutive days with psilocybin (1 mg/kg), LSD (0.08 mg/kg), or saline and then tested in DRL 72s for the following 4 weeks. Results: Treatment with psilocybin but not LSD demonstrated an immediate antidepressant-like effect, manifested as an increased number of reinforced presses and response efficiency. By contrast, neither of the drugs showed a long-term (up to 4 weeks following administration) antidepressant-like effect. Conclusions: Using DRL 72s schedule of reinforcement, we demonstrated the acute antidepressant-like effect of psilocybin but not of LSD, and failed to detect their persistent antidepressant-like efficacy. The present study suggests that the detection of long-lasting antidepressant-like activity in rats could be challenging and may require entirely novel behavioral methods.