title: Effects of lorazepam and WAY-200070 in larval zebrafish light/dark choice test.
abstract: 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.
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Chen
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Cuizhen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: gangpeng@fudan.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000378:metabolism; D019262:Habenula / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007814:Larva; D008027:Light; D008140:Lorazepam / Q000494:pharmacology*; D023421:Models, Animal; D009483:Neuropsychological Tests; D010080:Oxazoles / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: C556295:4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol; C436045:4-dihydroxyborylphenylalanine; D014151:Anti-Anxiety Agents; D001896:Boron Compounds; D047629:Estrogen Receptor beta; D010080:Oxazoles; D010636:Phenols; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D011743:Pyrimidines; C502077:WAY 200070; D029961:Zebrafish Proteins; C074283:estradiol 3-benzoate; D010649:Phenylalanine; D004958:Estradiol; D008140:Lorazepam; D003975:Diazepam
keywords: Anxiety; Benzodiazepines; Estrogen receptor beta; Habenula; Zebrafish