Abstract: 【Objective】 To explore the cellular distribution of cannabinoid 1 receptor (CB1R) in the central nervous system (CNS) of C57B/L6 mice. Detect the level of CB1R expression during experimental autoimmune encephalomyelitis (EAE). To study the immunomodulation of EAE by CB1R Antagonist. 【Methods】 Prepared hippocampal neurons from C57B/L6 mice embryos (E18) and glia cells from C57B/L6 mice neonatal cortex (postnatal day 1). Mice were grouped randomly as normal group

complete Freunds adjuvant (CFA) group

EAE mice were grouped randomly as vehicle control group and CB1R antagonist (SR141716A

SR1) group. Clinical scores and body weight were recorded during the course of EAE. We detected the expression of CB1R by SYBR Green-based real time PCR

western-blot and immunostaining. The levels of cytokines (IL-1β

IL-4

IL-10

IL-17

IL-6

TNF-α

and IFN-γ) were measured by ELISA. 【Results】 CB1R was observed in neurons and microglia but barely detected in astrocytes. CB1R decreased significantly in neurons

while increased in microglia significantly. The level of CB1R expression in spleens did not show a significant difference compared with CFA-immunized mice. SR1 accelerates onset of EAE; SR1 up-regulated the expression of IL-17

TNF-α

IL-1β and IL-6 in the CNS and the periphery. 【Conclusion】 CB1R expressed in neurons and microglia. SR1 participate in the immune regulation in the CNS and the periphery. CB1R could play a prominent role in neuroprotection and immuomodulation.