Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects -- Jiang et al., 10.1172/JCI25509 -- Journal of Clinical Investigation (2006)

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
by: Jiang et al.

Journal of Clinical Investigation, 10.1172/JCI25509 (2006)

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

Wen Jiang ¹, Yun Zhang ², Lan Xiao ², Jamie Van Cleemput ², Shao-Ping Ji ², Guang Bai ³, Xia Zhang ⁴^*

¹ Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China. ² Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. ³ Department of Biomedical Sciences, Dental School, Program in Neuroscience, University of Maryland, Baltimore, Maryland, USA. ⁴ Neuropsychiatry Research Unit, 103 Wiggins Road, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4. Phone: (306) 966-2288; Fax: (306) 966-8830

^* Address correspondence to: E-mail: zhangxia{at}duke.usask.ca

Received for publication April 29, 2005, and accepted in revised form August 9, 2005

Abstract

The hippocampal dentate gyrus in the adult mammalian brain containsneural stem/progenitor cells (NS/PCs) capable of generatingnew neurons, i.e., neurogenesis. Most drugs of abuse examinedto date decrease adult hippocampal neurogenesis, but the effectsof cannabis (marijuana or cannabinoids) on hippocampal neurogenesisremain unknown. This study aimed at investigating the potentialregulatory capacity of the potent synthetic cannabinoid HU210on hippocampal neurogenesis and its possible correlation withbehavioral change. We show that both embryonic and adult rathippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors,indicating that cannabinoids could act on CB1 receptors to regulateneurogenesis. This hypothesis is supported by further findingsthat HU210 promotes proliferation, but not differentiation,of cultured embryonic hippocampal NS/PCs likely via a sequentialactivation of CB1 receptors, G_i/o proteins, and ERK signaling.Chronic, but not acute, HU210 treatment promoted neurogenesisin the hippocampal dentate gyrus of adult rats and exerted anxiolytic-and antidepressant-like effects. X-irradiation of the hippocampusblocked both the neurogenic and behavioral effects of chronicHU210 treatment, suggesting that chronic HU210 treatment producesanxiolytic- and antidepressant-like effects likely via promotionof hippocampal neurogenesis.

Full Research Article at JCI

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