Ketamine Exposure Attenuates Social Avoidance Behavior Following Social Defeat Stress in Adolescence

RM-215-218

Nearly 8% of children and adolescents suffer from Major Depressive Disorder (MDD). However, the current available pharmacological treatments improve symptoms in only a small portion of this depressed population. Ketamine, an anesthetic, has been recently proposed for the treatment of clinical depression due to its effectiveness as a rapid-acting antidepressant in adult MDD patients. Despite this, it is not yet known whether ketamine is an effective treatment for mood-related disorders in adolescent populations. Thus, to assess the potential fast-acting antidepressant-like properties of ketamine in juveniles, we exposed adolescent male mice to 10 days of social defeat stress (postnatal days 35-44) a behavioral procedure that it commonly used to study depression at the preclinical level. Immediately after the final stress episode, mice received either ketamine (20 mg/kg) or saline. On the following day (postnatal day 45), mice were screened for social avoidance behavior. As expected, saline pretreated mice (controls) displayed a depressive-like behavior phenotype, as inferred from increased avoidant behavior. Conversely, ketamine-treated mice spent more time interacting with a social target, and were less avoidant, when compared to their control counterparts. Collectively, this indicates that ketamine reversed the depressive-like behavior observed after chronic exposure to social stressors in adolescent C57BL/6 mice. As such, our data suggest that ketamine may be an effective treatment for adolescent MDD.