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 atinvestigating the potential regulatory capacity ofthe 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 onCB1 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.
