Fear extinction learning and retention during adolescence in rats and mice: a systematic review

Despite exposure-based treatments being recommended for anxiety disorders, these treatments are ineffective for over half of all adolescents who receive them. The limited efficacy of exposure during adolescence may be driven by a deficit in extinction. Although indications of diminished extinction learning during adolescence were first reported over 10 years ago, these findings have yet to be reviewed and compared. This review (k = 34) found a stark inter-species difference in extinction performance: studies of adolescent mice reported deficits in extinction learning and retention of both cued and context fear. In contrast, studies of adolescent rats only reported poor extinction retention specific to cued fear. Adolescent mice and rats appeared to have only one behavioral outcome in common, being poor extinction retention of cued fear. These findings suggest that different behavioral phenotypes are present across rodent species in adolescence and highlight that preclinical work in rats and mice is not interchangeable. Further investigation of these differences offers the opportunity to better understand the etiology, maintenance, and treatment of fear-based disorders.