Early-Life Exposure to Ketamine Alters Risk-Taking Behavior in Adulthood

Early-life exposure to ketamine mediates an anxiolytic effect in adulthood. Epidemiological reports indicate mood-related disorders, such as depression, are among the most severe and potentially incapacitating forms of psychiatric illnesses affecting individuals across the world. Interestingly, depression has only been recognized to affect children and adolescents until recent years, and as a result, the long-term effects of pharmacological treatments for this particular condition have not been thoroughly assessed. Recently, ketamine, an N-methyl-D-Aspartate receptor antagonist, has been proposed as a possible antidepressant treatment showing rather rapid-acting and long-lasting effects, when compared to other traditional pharmacological agents, such as selective serotonin reuptake inhibitors. Thus, research that sheds light into the potential longlasting effects of ketamine, in an age-specific manner, is warranted - especially when considering ketamine’s abuse potential. To address this issue, we exposed adolescent c57BL/6 mice to ketamine (0 or 20 mg/kg) once a day for 15 consecutive days, [postnatal day (PD) 35-49]. Twenty-one days later (PD70), they were tested on behavioral responses to aversive-inducing situations. Specifically, their behavioral reactivity to the elevated plus-maze (EPM), a paradigm used to assess anxiogenic behavior, was examined. The results of this experiment showed that adult mice exposed to ketamine during adolescence spent more time in the open arms of the EPM, thus, displaying a long-lasting anxiolytic effect. As such, our results indicate that exposure to ketamine during adolescence decreases vulnerability to anxietyeliciting situations in adulthood