TY - JOUR
T1 - Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments
AU - Connors, Kristin A.
AU - Valenti, Theodore W.
AU - Lawless, Kelly
AU - Sackerman, James
AU - Onaivi, Emmanuel S.
AU - Brooks, Bryan W.
AU - Gould, Georgianna G.
N1 - Funding Information:
We thank Krista Prosser and the Brooks lab group for assistance with zebrafish behavioral studies, and Dr. Lynette Daws and Dr. Alan Frazer for the use of their laboratory facilities for autoradiography studies. This project was supported by Grant No. MH086708 (to GG) and DA032890 (to EO) from the National Institutes of Health, a sub-award from Grant No. T42/CCT610417 from the National Institute for Occupational and Environmental Health (NIOSH)/Centers for Disease Control and Prevention (CDC) to the Southwest Center for Occupational and Environmental Health (SWCOEH), a NIOSH Education and Research Center (to GG), and by the Glasscock Fund for Excellence in Environmental Science (to KC), and Department of Environmental Science at Baylor University (to BB). Undergraduate student involvement was supported by funds from the office of Dean Sandra DeYoung at William Paterson University .
PY - 2014/6
Y1 - 2014/6
N2 - The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitalizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [3H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of similarly Gαi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176±8, 275±32, and 230±36fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [3H] WIN55,212-2 binding density was higher in those same brain regions at 6±0.3, 5.5±0.4 and 7.3±0.3pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50mg/L), or dietary exposure to WIN55,212-2 (7μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p<0.05). Acute exposure to WIN55,212-2 at 0.5-50mg/L reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future.
AB - The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitalizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [3H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of similarly Gαi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176±8, 275±32, and 230±36fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [3H] WIN55,212-2 binding density was higher in those same brain regions at 6±0.3, 5.5±0.4 and 7.3±0.3pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50mg/L), or dietary exposure to WIN55,212-2 (7μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p<0.05). Acute exposure to WIN55,212-2 at 0.5-50mg/L reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future.
KW - Anxiety
KW - Aquatic exposure
KW - Autoradiography
KW - Cannabinoid
KW - Gαi/o coupled receptors
KW - Inhibition
KW - Light/dark preference
KW - Scototaxis
KW - Serotonin
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U2 - 10.1016/j.aquatox.2013.12.005
DO - 10.1016/j.aquatox.2013.12.005
M3 - Article
C2 - 24411165
AN - SCOPUS:84899493174
SN - 0166-445X
VL - 151
SP - 105
EP - 113
JO - Aquatic Toxicology
JF - Aquatic Toxicology
ER -