Behavioral and physiological effects of acute ketamine exposure in adult zebrafish

Neurotoxicol Teratol. Nov-Dec 2011;33(6):658-67. doi: 10.1016/ Epub 2011 Jun 13.


Ketamine is a non-competitive glutamatergic antagonist used to induce sedation and analgesia. In sub-anesthetic doses, it induces hyperlocomotion, impairs memory and evokes stereotypic circling in rodents. Zebrafish (Danio rerio) emerged as a promising new animal model to screen the effects of psychotropic compounds. Here, we investigated the effects of sub-anesthetic doses of ketamine on anxiety, locomotion, habituation and social behavior of adult zebrafish. Acute 20-min exposure to 20 and 40 mg/L (but not 2 mg/L) of ketamine reduced anxiety, impaired intra-session habituation, evoked circular swimming and disrupted zebrafish shoaling. Additionally, ketamine reduced whole-body cortisol levels and elevated brain c-fos expression in zebrafish. Our findings demonstrate the sensitivity of zebrafish to behavioral and physiological effects of sub-anesthetic doses of ketamine, further supporting the utility of this species as a model for neuropharmacological research, including testing ketamine and related drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Amino Acid Antagonists / toxicity
  • Female
  • Gene Expression / drug effects
  • High-Throughput Screening Assays
  • Hydrocortisone / metabolism
  • Ketamine / pharmacology*
  • Ketamine / toxicity
  • Male
  • Motor Activity / drug effects
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-fos / genetics
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Video Recording
  • Zebrafish / metabolism
  • Zebrafish / physiology*


  • Excitatory Amino Acid Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Hydrocortisone