Preclinical Behavioral and Pharmacological Treatments for Enhancing Fear Extinction in Adolescence

Adolescence is a window of vulnerability for the development of anxiety disorders but also a window of opportunity for treatments to minimize the long-term impact of such disorders. Current first-line treatments, primarily exposure-based cognitive-behavioral therapy (CBT), have limited long-term efficacy in adolescents. The urgent need for more effective interventions is underscored by the frequent reports of extinction impairments in adolescents as well as the rising anxiety rates in youth, particularly post-COVID-19. Preclinical research on the extinction of learned fear in adolescents may contribute to developing better treatment approaches to anxiety in this age group. Unfortunately, this is still a largely under-explored area. However, both pharmacological and behavioral augmentation strategies can be used to enhance extinction learning and consolidation. Here we describe work exploring such adjuncts, focusing on pre-clinical work with rodents. Much of the research to date shows striking developmental differences in response to various pharmacological treatments, with only a few shown to be effective in adolescents. Further, recent experience of stress reduces the efficacy of these treatments in adolescence. This review highlights the necessity for tailored strategies, especially when it comes to pharmacological adjuncts, that address developmental differences in drug responses as well as the impact of stressful experiences on treatment efficacy.