Neurobiological, behavioral, and cognitive effects of ketamine in adolescents: A review of human and pre-clinical research

Behav Brain Res. 2022 Oct 28;435:114049. doi: 10.1016/j.bbr.2022.114049. Epub 2022 Aug 8.

Abstract

S-ketamine is approved for treatment-resistant patients with depression and adult patients with suicide behavior. While ketamine is therapeutically beneficial in adults, there is a dearth of research on the effects of ketamine on adolescent brain function and behavior. In this review we summarize the current literature on the neurobiological and behavioral effects of adolescent ketamine exposure in preclinical animal models and humans. A search of PubMed was conducted using pre-defined criteria, resulting in the evaluation of 406 articles. A total of 39 animal studies and 7 human studies met the selection criteria. The included studies examined the effects of ketamine exposure during adolescence and excluded studies on ketamine use for pain or anesthesia and ketamine as a model of schizophrenia. Pre-clinical animal models of adolescent ketamine exposure show ketamine-induced neurotoxicity and apoptosis, and changes in locomotor activity, social behaviors, anxiety- and depression-like behaviors, and memory. There is variability in the results, and differences in ketamine dose and length of exposure appears to influence the results. Ketamine reduces symptoms of depression and anxiety and improves mood in human adolescents. Much of the literature on adolescent ketamine exposure examines the effects in males, with more limited research in females. Relatively little research has focused on adolescent ketamine exposure. Despite its effectiveness for mitigating symptoms of depression, adolescent ketamine exposure can disrupt memory and other behaviors and have deleterious effects on brain function. Further research is warranted to better define doses and dosing paradigms that are beneficial without unintended side effects in adolescence.

Keywords: Adolescence; Anxiety-like behavior; Depression-like behavior; Ketamine; Long-term potentiation; Memory.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy
  • Behavior, Animal
  • Cognition
  • Depression / chemically induced
  • Depression / drug therapy
  • Female
  • Humans
  • Ketamine*
  • Male

Substances

  • Ketamine