Acute effect of Δ-9-tetrahydrocannabinol on neuromuscular transmission and locomotive behaviors in larval zebrafish

J Neurophysiol. 2023 Apr 1;129(4):833-842. doi: 10.1152/jn.00438.2022. Epub 2023 Mar 8.

Abstract

Given the increasing trend of cannabis use for recreational and therapeutic purposes, a comprehensive examination of cannabis effects is warranted. The principal psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), is a potent disrupter of neurodevelopment. Nevertheless, the impact of acute exposure to THC on developing motor systems is not well-investigated. In this study, using a neurophysiological whole cell patch clamp approach we demonstrated that a 30-min exposure to THC can alter spontaneous synaptic activities at neuromuscular junctions of 5-day post-fertilized zebrafish. An increased frequency of synaptic activity and altered decay kinetic properties were documented in the THC-treated larvae. Locomotive behaviors, including swimming activity rate and C-start escape response to sound were also affected by THC. Although the THC-treated larvae displayed hyperactivity of their basal swimming levels, their escape response rate to sound stimuli was reduced. These findings suggest that acute exposure to THC can disrupt neuromuscular transmission and locomotor-driven responses in developing zebrafish.NEW & NOTEWORTHY Acute exposure to THC alters motor neuron-muscle communication and motor behaviors in developing zebrafish. Our neurophysiology data indicated that the properties of spontaneous synaptic activity at neuromuscular junctions, such as decay component of acetylcholine receptors and frequency of synaptic events, were affected by a 30-min exposure to THC. Hyperactivity and reduced responsiveness to the sound stimulus were also observed in the THC-treated larvae. Exposure to THC during early developing stages may induce motor dysfunction.

Keywords: acute exposure; developing larvae; locomotor function; neuromuscular transmission; Δ-9-tetrahydrocannabinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists
  • Dronabinol* / pharmacology
  • Motor Neurons
  • Synaptic Transmission
  • Zebrafish*

Substances

  • Dronabinol
  • Cannabinoid Receptor Agonists