Fishing for Answers
Clues from zebrafish suggest a key role for cannabinoid receptor 2 in behavior
Matthew Hallam |
The zebrafish (Danio rerio) has a long history as a model organism in genetics studies, thanks to its quick reproductive cycle, small size, and the similarity of their genetic makeup to human systems.
Agnes Acevedo-Canabal and colleagues recently used this unique organism to investigate how cannabinoid receptor 2 (CB2), a component of the endocannabinoid system, affects behavior (1). CB2 is thought to be the receptor responsible for many of the medicinal properties of cannabis, in part due to its role in reducing inflammation.
The team used CRISPR-Cas9 technology to produce zebrafish offspring lacking functional CB2 receptors (‘CB2 knockouts’) and compared their behaviors with those of normal (‘wildtype’) zebrafish in a number of tests, including assessment of their responses to light and their tendency to occupy a predefined central area of their tank. The tests were then repeated while exposing the fish to two drugs: valproic acid, an anxiety-reducing drug, and pentylenetetrazol, an anxiety-inducing drug.
A number of differences were observed in the behavior of the CB2 knockout fish versus their wild-type counterparts. First, CB2 knockout fish travelled significantly less when exposed to light and significantly more in the dark. Second, CB2 knockout fish avoided the center of the tank, preferring to stick to the edges. And third, they were affected differently by the drugs administered; valproic acid did less to reduce swimming activity in CB2 knockouts, for example, while pentylenetetrazol led to increased hyperactivity among knockout fish when transitioning from dark to light.
The authors write, “We showed that larvae lacking CB2 behave differently in complex behaviors that can be assimilated to anxiety-like behaviors. Mutant larvae responded differently to valproic acid and pentylenetetrazol treatments, providing in vivo evidence of CB2 modulating complex behaviors.” The research provides new clues to the wide-reaching functions of cannabinoid receptors, and the authors add that their approach could potentially be scaled up for use in drug discovery.
- A Acevedo-Canabal et al., “Altered swimming behaviors in zebrafish larvae lacking cannabinoid receptor 2,” Cannabis Cannabinoid Res, Online ahead of print, DOI: 10.1089/can.2018.0025, (2019).