Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish
Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual....
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doaj-fe8b7a75d6044c82a22163c9ebe5027c2021-02-20T00:05:01ZengMDPI AGBiomolecules2218-273X2021-02-011131931910.3390/biom11020319Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant ZebrafishJudit García-González0Bruno de Quadros1William Havelange2Alistair J. Brock3Caroline H. Brennan4School of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, UKSchool of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, UKSchool of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, UKLeica Biosystems Newcastle Ltd, Newcastle NE12 8EW, UKSchool of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, UKSynthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (<i>DISC1) </i>is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 mM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether <i>disc1</i> moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in <i>disc1</i> increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by <i>disc1</i>.https://www.mdpi.com/2218-273X/11/2/319zebrafishcannabinoids<i>disc1</i>JWH-018forced light/dark assayanxiety |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Judit García-González Bruno de Quadros William Havelange Alistair J. Brock Caroline H. Brennan |
spellingShingle |
Judit García-González Bruno de Quadros William Havelange Alistair J. Brock Caroline H. Brennan Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish Biomolecules zebrafish cannabinoids <i>disc1</i> JWH-018 forced light/dark assay anxiety |
author_facet |
Judit García-González Bruno de Quadros William Havelange Alistair J. Brock Caroline H. Brennan |
author_sort |
Judit García-González |
title |
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish |
title_short |
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish |
title_full |
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish |
title_fullStr |
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish |
title_full_unstemmed |
Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (<i>disc1</i>) Mutant Zebrafish |
title_sort |
behavioral effects of developmental exposure to jwh-018 in wild-type and disrupted in schizophrenia 1 (<i>disc1</i>) mutant zebrafish |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-02-01 |
description |
Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (<i>DISC1) </i>is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 mM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether <i>disc1</i> moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in <i>disc1</i> increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by <i>disc1</i>. |
topic |
zebrafish cannabinoids <i>disc1</i> JWH-018 forced light/dark assay anxiety |
url |
https://www.mdpi.com/2218-273X/11/2/319 |
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