Ketamine can effectively treat depression, but whether depressed patients with alcohol use disorder can safely use ketamine repeatedly remains unclear clinically. To investigate this possibility, Mohamed Kabbaj and colleagues from Florida State University modeled aspects of human depression in rats using long-term isolation and assessed how isolation and alcohol exposure alter ketamine intake. The authors found that a history of isolation and alcohol use influence the rewarding properties of ketamine in a sex-dependent manner.
Female rats took ketamine more than males in general. Prior alcohol use increased female rat ketamine intake while subsequently changing synapse structure in a reward-related brain region. In males, previous alcohol use and social isolation independently increased ketamine intake. Males that consumed alcohol during social isolation also experienced different synaptic changes in the reward-related brain region during ketamine intake than males who did not have alcohol during isolation. This work suggests that clinicians should consider sex differences and alcohol use history when using ketamine to treat patients. According to the authors, this eNeuro study is informative for clinical research and treatment of major depressive disorder.
