PUBLICATION
Behavioral, endocrine, and neuronal alterations in zebrafish (Danio rerio) following sub-chronic coadministration of fluoxetine and ketamine
- Authors
- Pittman, J., Hylton, A.
- ID
- ZDB-PUB-150826-5
- Date
- 2015
- Source
- Pharmacology, biochemistry, and behavior 139 Pt B: 158-62 (Journal)
- Registered Authors
- Pittman, Julian
- Keywords
- Anxiety, Depression, Fluoxetine, Ketamine, Zebrafish (Danio rerio)
- MeSH Terms
-
- Animals
- Antidepressive Agents, Second-Generation/administration & dosage
- Anxiety/drug therapy
- Behavior, Animal/drug effects*
- Behavior, Animal/physiology
- Brain/drug effects
- Brain/physiology
- Depression/drug therapy
- Disease Models, Animal
- Drug Interactions
- Drug Therapy, Combination
- Ethanol/administration & dosage
- Excitatory Amino Acid Antagonists/administration & dosage
- Female
- Fluoxetine/administration & dosage*
- Hydrocortisone/metabolism
- Ketamine/administration & dosage*
- Male
- Zebrafish/physiology*
- PubMed
- 26303305 Full text @ Pharmacol. Biochem. Behav.
Citation
Pittman, J., Hylton, A. (2015) Behavioral, endocrine, and neuronal alterations in zebrafish (Danio rerio) following sub-chronic coadministration of fluoxetine and ketamine. Pharmacology, biochemistry, and behavior. 139 Pt B:158-62.
Abstract
Most existing pharmacological treatments have focused on the 'monoamine hypothesis' for targeted drug design for major depressive disorder (MDD). Many of these medications have a delayed onset-of-action and limited efficacy. Antidepressants with principal targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. Growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Ketamine (Ketalar®) is a non-competitive glutamatergic antagonist classically used to induce sedation. However, preliminary clinical evidence has been promising with regard to its rapidly acting antidepressant profile. Zebrafsh (Danio rerio) have emerged as a promising new animal model to screen the effects of numerous psychotropic compounds. This study aimed to determine if a sub-chronic low (sub-anesthetic) dose of ketamine could be used to augment the antidepressant effects of the widely used antidepressant fluoxetine (Prozac®) in adult zebrafish, employing an ethanol withdrawal model. Sub-chronic exposure to dosages of 100μg/L fluoxetine and 20mg/L of ketamine reduced anxiety/depression-like behaviors, lead to upregulation of serotonin synthesis and elevated whole-body cortisol levels. These results demonstrate the utility of zebrafish as a model for neuropharmacological research, and the possible efficacy of fluoxetine and ketamine coadminstration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping