ZFIN ID: ZDB-PUB-150407-7
Effects of lorazepam and WAY-200070 in larval zebrafish light/dark choice test
Chen, F., Chen, S., Liu, S., Zhang, C., Peng, G.
Date: 2015
Source: Neuropharmacology 95: 226-33 (Journal)
Registered Authors: Chen, Fengjiao, Chen, Sijie, Peng, Gang, Zhang, Cuizhen
Keywords: anxiety, benzodiazepines, estrogen receptor beta, habenula, zebrafish
MeSH Terms:
  • Animals
  • Anti-Anxiety Agents/pharmacology*
  • Anxiety/drug therapy*
  • Anxiety/metabolism
  • Boron Compounds/pharmacology
  • Choice Behavior/drug effects
  • Choice Behavior/physiology
  • Diazepam/pharmacology
  • Estradiol/analogs & derivatives
  • Estradiol/pharmacology
  • Estrogen Receptor beta/metabolism
  • Habenula/drug effects
  • Habenula/metabolism
  • Hypothalamus/drug effects
  • Hypothalamus/metabolism
  • Larva
  • Light
  • Lorazepam/pharmacology*
  • Models, Animal
  • Neuropsychological Tests
  • Oxazoles/pharmacology*
  • Phenols/pharmacology*
  • Phenylalanine/analogs & derivatives
  • Phenylalanine/pharmacology
  • Proto-Oncogene Proteins c-fos/metabolism
  • Pyrazoles/pharmacology
  • Pyrimidines/pharmacology
  • Visual Perception/drug effects
  • Visual Perception/physiology
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 25842247 Full text @ Neuropharmacology
Zebrafish larvae spend more time in brightly illuminated area when placed in a light/dark testing environment. Here we report that the anxiolytic drugs lorazepam and diazepam increased the time larval fish spent in the dark compartment in the light/dark test. Lorazepam did not affect the visual induced optokinetic response of larval fish. Gene expression levels of c-fos and crh were significantly increased in the hypothalamus of fish larvae underwent light/dark choice behavior, whilst lorazepam treatment alleviated the increased c-fos and crh expressions. Furthermore, we found estrogen receptor β gene expression level was increased in fish larvae underwent light/dark choice. We next examined effects of estrogen receptor modulators (estradiol, BPA, PHTPP, and WAY-200070) in the light/dark test. We identified WAY-200070, a highly selective ERβ agonist significantly altered the light/dark choice behavior of zebrafish larvae. Further investigation showed WAY-200070 treatment caused a reduction of crh expression level in the hypothalamus, suggesting activation of ERβ signaling attenuate the stress response. Interestingly, WAY-200070 treatment caused marked increase of c-fos expression in the habenula of fish larvae underwent behavior test. These results suggest WAY-200070 activation of ERβ mediated signaling may regulate anxiety related behavior in zebrafish through modulation of neuronal activity in habenula.