Rationale Ketamine has emerged as a rapid-acting antidepressant drug for treatment-resistant depression in adults and is currently evaluated for adolescent depression. However, the long-term effects of ketamine exposure during this period of brain development remain unclear, particularly regarding addiction liability. Objectives To investigate whether repeated ketamine exposure during adolescence may influence the long-term risk of addiction following subsequent exposure to commonly abused drugs (alcohol and cocaine) in adulthood. Methods Male and female Sprague-Dawley rats received daily i.p. injections of ketamine (10 mg/kg) or saline for 7 consecutive days during mid adolescence. The dose paradigm of ketamine administered was selected based on its antidepressant-like properties in adolescent rats. In adulthood, addiction liability was measured by voluntary ethanol consumption, using a two-bottle choice paradigm, and by assessing cocaine reward using a single-exposure place preference protocol. Results The main results suggested that a therapeutic dose of ketamine exposure during adolescence did not enhance addictive liability in adulthood as measured by voluntary ethanol consumption or cocaine reward in rats of both sexes. Conclusions Ketamine, administered during adolescence at a dose known to induce antidepressant-like effects did not impact the long-term risk of addiction caused by exposure to commonly abused drugs (i.e., alcohol and cocaine). These results suggested a good long-term safety profile following the therapeutic use of ketamine in adolescence.
