C10: Age-Related Differences in Rat Behavioral Responses to Psilocybin

The prevalence of adolescent depression is at an all-time high. Pharmacological treatments are similar to adults but elicit different—and oftentimes adverse—consequences in adolescents, including anxiety and suicidal ideations. Thus, significant demand exists for improved therapeutic interventions for this age group. Psilocybin, a serotonergic agonist, has demonstrated potential for therapeutic efficacy in adulthood; however, its effects have not been evaluated in adolescents. Therefore, the purpose of this study is to investigate age-related differences in psilocybin efficacy. Additionally, we sought to determine whether adolescent treatment of psilocybin has long-term effects on anxiety-associated behaviors and decision-making. In separate groups of rats (10-11 per group), head twitch responses were quantified following administration of 1 mg/kg psilocybin or vehicle via gavage in early adolescence (35 days old) or late adolescence (45 days old) as well as in adulthood (110+ days old). In adulthood, adolescent-treated subjects completed an elevated zero maze and a novel object test to measure long-term effects of psilocybin on anxiety-associated behaviors. Lastly, animals underwent a reversal learning paradigm to assess effects on behavioral flexibility. Results demonstrate weaker acute responses to psilocybin in adolescents than adults (fewer head twitches), however no long term effects were noted in the elevated zero maze, novel object, or reversal learning paradigm after adolescent psilocybin administration. The pattern of acute effects suggests age-related differences in 5-HT2A/2C levels, which will be examined in future studies. Combined, these results imply that age-related differences in drug efficacy should be considered when evaluating the therapeutic efficacy of psilocybin or other psychedelic drugs, and that lasting changes in behavior may occur following adolescent treatment. This project will be completed to earn my honors with distinction, and has greatly influenced my decision to pursue a graduate degree in neuroscience or pharmacology going forward.

Author(s): Alexia Zylko, Biology and Neuroscience Major

Advisor(s): Matthew McMurray, Department of Psychology