Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
Wen Jiang, Yun Zhang, Lan Xiao, Jamie Van Cleemput, Shao-Ping Ji, Guang Bai, Xia Zhang
Wen Jiang, Yun Zhang, Lan Xiao, Jamie Van Cleemput, Shao-Ping Ji, Guang Bai, Xia Zhang
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3104-3116. doi:10.1172/JCI25509.
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Categories: 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 chronic HU210 on the NSF test, the FST, and cell proliferatio...

Figure 8

Effects of chronic HU210 on the NSF test, the FST, and cell proliferation in the dentate gyrus. After receiving chronic vehicle, AM281, or HU210 injections for 10 days, rats were injected with BrdU to label dividing cells, followed 1 month later by behavioral testing and 1 day later by perfusion (n = 7–8 for each group in A–C; n = 5 for each group in D–F). (A) In the NSF test, rats receiving chronic HU210 (but not AM281) showed significantly shortened latency to feed in a novel environment but not in their home cages, suggesting anxiolytic effects produced by HU210. (B) In the FST, chronic HU210 (but not AM281) significantly shortened the duration of immobility (i.e., antidepressant-like effects). (C) Among the rats receiving vehicle, AM281, and HU210, there was no significant difference in the number climbing in the first 5 minutes in the pretest sessions of the FST. (D) Irradiation of the hippocampus prominently reduced cell proliferation in the SGZ. (E) Irradiation of the hippocampus blocked chronic HU210–induced shortened latency of rats to feed in novel environment but not in their home cages in the NSF test. (F) Irradiation of the hippocampus prevented chronic HU210–induced shortened duration of immobility in the FST. Error bars represent SEM. *P < 0.05 and **P < 0.01 by Tukey post-hoc tests after 1-way ANOVA.