Evaluating whether a therapeutic dose of ketamine exposure during adolescence influences adult vulnerability in rats to commonly abused drugs.

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.