ABSTRACT
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.
Subject(s)
Behavior, Animal/drug effects , Brain/drug effects , Excitatory Amino Acid Antagonists/pharmacology , Ketamine/pharmacology , Zebrafish/physiology , Animals , Anxiety/chemically induced , Brain/metabolism , Dose-Response Relationship, Drug , Excitatory Amino Acid Antagonists/toxicity , Female , Gene Expression/drug effects , High-Throughput Screening Assays , Hydrocortisone/metabolism , 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/metabolismABSTRACT
3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is a potent psychedelic drug inducing euphoria and hypersociability in humans, as well as hyperactivity and anxiety in rodents. Adult zebrafish (Danio rerio) have become a widely used species in neurobehavioral research. Here, we explore the effects of a wide range (0.25-120 mg/l) of acute MDMA doses on zebrafish behavior in the novel tank test. Although MDMA was inactive at lower doses (0.25-10 mg/l), higher doses reduced bottom swimming and immobility (40-120 mg/l) and impaired intrasession habituation (10-120 mg/l). MDMA also elevated brain c-fos expression, collectively confirming the usage of zebrafish models for screening of hallucinogenic compounds.
Subject(s)
Behavior, Animal/drug effects , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Animals , Brain Chemistry/drug effects , Dose-Response Relationship, Drug , Female , Male , Motor Activity/drug effects , Proto-Oncogene Proteins c-fos/analysis , ZebrafishABSTRACT
Zebrafish (Danio rerio) are becoming increasingly popular in neurobehavioral research. Here, we summarize recent data on behavioral responses of adult zebrafish to a wide spectrum of putative anxiolytic and anxiogenic agents. Using the novel tank test as a sensitive and efficient behavioral assay, zebrafish anxiety-like behavior can be bi-directionally modulated by drugs affecting the gamma-aminobutyric acid, monoaminergic, cholinergic, glutamatergic and opioidergic systems. Complementing human and rodent data, zebrafish drug-evoked phenotypes obtained in this test support this species as a useful model for neurobehavioral and psychopharmacological research.
