Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments
- Authors
- Connors, K.A., Valenti, T.W., Lawless, K., Sackerman, J., Onaivi, E.S., Brooks, B.W., and Gould, G.G.
- ID
- ZDB-PUB-140317-19
- Date
- 2014
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 151: 105-13 (Journal)
- Registered Authors
- Gould, Georgianna, Lawless, Kelly
- Keywords
- Anxiety, Aquatic exposure, Autoradiography, Cannabinoid, Gαi/o coupled receptors, Inhibition, Light/dark preference, Scototaxis, Serotonin
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Protein Binding/drug effects
- Receptors, Cannabinoid/metabolism*
- Receptors, Serotonin/metabolism*
- Selective Serotonin Reuptake Inhibitors/toxicity*
- Water Pollutants, Chemical/toxicity*
- Zebrafish/physiology*
- PubMed
- 24411165 Full text @ Aquat. Toxicol.
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 Gμi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176 ± 8, 275 ± 32, and 230 ± 36 fmol/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 ± 0.3 pm/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 (50 mg/L), or dietary exposure to WIN55,212-2 (7 μg/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 0.5–50 mg/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.