Cannabinoids shaped brain activity and new neuron growth in zebrafish

CB1 receptors were found in glutamatergic neurons of the zebrafish pallium. Blocking CB1 with rimonabant reduced spontaneous excitatory activity and ERK phosphorylation, suggesting CB1 maintains tonic excitatory signaling. Acute cannabinoid exposure reduced neural stem cell proliferation, but during the maturation window (12-24 days), cannabinoid treatment increased the number of surviving new neurons, an effect reversed by rimonabant.

Researchers mapped CB1 receptor expression in the zebrafish pallium using immunofluorescence and single-cell mRNA analysis. Electrophysiology measured synaptic activity with and without rimonabant. Neural stem cell proliferation was assessed after acute cannabinoid exposure, and neuronal maturation was tracked using BrdU labeling over 25 days with cannabinoid treatment during the 12-24 day maturation window.

The zebrafish brain undergoes continuous adult neurogenesis, making it a powerful model for understanding how cannabinoids affect new brain cell formation. The finding that cannabinoids reduce initial stem cell proliferation but increase neuron survival suggests a complex regulatory role that may be relevant to mammalian brains.

This study reveals a conserved role for the endocannabinoid system in regulating neurogenesis across vertebrates. The dual effect (suppressing proliferation but enhancing survival) mirrors some findings in mammalian studies and suggests the endocannabinoid system may act as a quality control mechanism for new neuron integration.

Zebrafish neurogenesis is far more robust than in adult mammals, so translation to human brains is uncertain. The specific cannabinoids used and their concentrations were not detailed in the abstract. Only acute and sub-chronic exposures were tested.