Psychedelic drugs that activate the 5-HT2A receptor show promise for treating psychiatric disorders like obsessive-compulsive disorder. In a mouse model of compulsive-like behavior (the marble burying test), the 5-HT2A receptor antagonist M100907 blocked the effect of the psychedelic DOI, and the 5-HT2C receptor antagonist SB242084 blocked the effect of citalopram, but neither antagonist blocked the effect of psilocybin. This confirms 5-HT2A receptor activation as a mechanism for reducing compulsive-like digging and suggests that 5-HT2A and 5-HT2C receptors can work in parallel. The results with psilocybin indicate that a mechanism independent of 5-HT2 receptors also contributes to its effect on repetitive digging.
Psychedelic-assisted psychotherapy shows promise for treating mental health disorders, and research on 5-HT2AR agonist psychedelics has grown rapidly. In humans, these compounds alter consciousness and affect emotional, social, and self-referential information processing. The translational value of animal behavior studies is debated. In rodents, acute psychedelic treatment produces head twitches, disrupts sensorimotor gating, stimulates motor activity, inhibits exploration, and shows anxiolytic-like effects while inhibiting repetitive behavior. Effects on depression-like behaviors, cognitive function, and social interaction are discrepant. Lasting effects are sensitive to experimental protocols. Improving animal studies by assessing lasting effects, publishing negative findings, and relating behaviors to neuroplastic changes will enhance translational value.