Journal
NEUROPHARMACOLOGY
Volume 95, Issue -, Pages 226-233Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.03.022
Keywords
Anxiety; Benzodiazepines; Estrogen receptor beta; Habenula; Zebrafish
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Funding
- National Natural Science Foundation of China [31171074]
- Pujiang Talent Project [09PJ1401900]
- National Natural Science Foundation of China [31171074]
- Pujiang Talent Project [09PJ1401900]
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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 beta 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 ER beta 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 ER beta 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 ER beta mediated signaling may regulate anxiety related behavior in zebrafish through modulation of neuronal activity in habenula. (C) 2015 Elsevier Ltd. All rights reserved.
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