Abstract
CB1 cannabinoid receptor (CB1R) activation stimulates neurogenesis in developing rat brain. Chronic ethanol treatment has been shown to inhibit developmental and adult brain neurogenesis. The objective of the present study is to determine if CB1R regulates ethanol‐mediated inhibition of developmental neurogenesis in zebrafish. We have used green fluorescence protein (GFP)‐expressing transgenic zebrafish (ISLET‐1) embryos to study neurogenesis using confocal microscopy. We have shown that zCB1R mRNA transcript is expressed in the different regions of zebrafish brain at 48 and 72 hpf (hour post‐fertilization). We also showed that CB1R agonist CP55940 (1–10 μM) treatment stimulated zCB1R expression and motor neurogenesis in zebrafish brain. We further showed knocking down CB1R using morpholino or antagonist‐mediated blockade of CB1R attenuated CB1R‐mediated increase in neurogenesis. Further we have found that chronic ethanol (0.5%–1.5%)‐treatment during embryonic development (6hpf–36 hpf) dose‐dependently reduced zCB1R expression and motor neurogenesis. Co‐treatment with CB1R agonist CP5540 or FAAH‐inhibitor URB597 attenuated ethanol‐mediated inhibition of developmental neurogenesis. Together, results from this study showed that zCB1R plays a vital role in the regulation developmental neurogenesis as well as ethanol‐mediated deleterious effects on neurogenesis.
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