Abstract
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 (DISC1) 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 μM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether disc1 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 disc1 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 disc1.
Highlights
Published: 19 February 2021Synthetic cannabinoids commercialized as “spice”, “K2”, “legal weed”, or “herbal incense” are man-made chemicals used as an alternative to marijuana
We addressed the following research questions: (1) does exposure to JWH-018 during development modulate behavior in larvae zebrafish, (2) are the effects of exposure to JWH-018 during development similar to the effects of term behavioral alterations [5]. Delta-9tetrahydrocannabinol (THC) or nicotine in wild-type larval zebrafish, and (3) are the acute and long-lasting effects of developmental exposure to JWH-018 or THC exacerbated by disc1 loss of function?
On transition from dark to light period, zebrafish larvae increased the distance travelled during the first seconds after the change in light; no differences were observed between JWH-018 treated and non-treated larvae (Figure 2B,C)
Summary
Synthetic cannabinoids commercialized as “spice”, “K2”, “legal weed”, or “herbal incense” are man-made chemicals used as an alternative to marijuana. They gained popularity during the early 2000s and were legal in many countries [1], with consumption prevalence ranging between 0.2% and 4% in the general population [2]. The endocannabinoid system plays an important role in early brain development [4]; consumption of cannabinoids (both natural or synthetic) during pregnancy may affect fetal neurodevelopment, leading to long-term behavioral alterations [5]. Delta-9tetrahydrocannabinol (THC), the major psychoactive component of cannabis, can cross the placental barrier [5], bind the cannabinoid receptors located in the fetus brain, and interfere with the endocannabinoid system affecting neurogenesis and neuronal migration [5]. Stronger effects on brain development may be produced by JWH-018 (1-pentyl-3(1-naphthoyl)-indole), one of the most common psychoactives in synthetic cannabinoids
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