Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
Wen Jiang, … , Guang Bai, Xia Zhang
Wen Jiang, … , Guang Bai, Xia Zhang
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3104-3116. https://doi.org/10.1172/JCI25509.
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Research Article Neuroscience

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects

Abstract

The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

Authors

Wen Jiang, Yun Zhang, Lan Xiao, Jamie Van Cleemput, Shao-Ping Ji, Guang Bai, Xia Zhang

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Effects of HU210 treatment on cell proliferation in the dentate gyrus in...
Effects of HU210 treatment on cell proliferation in the dentate gyrus in adult rats (n = 5–7 rats in each group). Cell proliferation was assessed by BrdU labeling of dividing cells. (A) Representative microphotographs of the dentate gyrus show BrdU-positive cells clustered or aggregated in the SGZ in rats receiving an acute injection of vehicle or 100 μg/kg of HU210. Scale bar, 60 μm. (B) There was no significant difference in the average number of BrdU-stained cells in the dentate gyrus per section following 1 dose of acute vehicle, 100 and 25 μg/kg of HU210, and 3 mg/kg of AM281. (C) Representative microphotographs of the dentate gyrus show that twice-daily injections of 100 μg/kg of HU210 for 10 days apparently increased the density of BrdU-positive cells in the SGZ relative to chronic vehicle injection. Scale bar, 60 μm. (D) Relative to vehicle injection, there was a significant increase in the number of BrdU-immunoreactive cells in the dentate gyrus following chronic treatment with 100 μg/kg of HU210, but not 25 μg/kg of HU210 or 3 mg/kg of AM281. Error bars represent SEM. *P < 0.05 by Tukey post-hoc tests after 1-way ANOVA.