The CB2 receptor inhibits microglial activation and the expression of proinflammatory cytokines in the SN in vivo. Animals that received vehicle as a control (a); MPTP (b); MPTP and WIN55,212-2 (c); MPTP and JWH-133 (d); MPTP, WIN55,212-2 and AM630 (e); or MPTP, JWH-133 and AM630 (f) were killed 3 days after the last MPTP injection. Brain tissues were cut, and SN tissues were immunostained with an antibody for MAC-1 to label microglia (a–f). Insets show higher magnifications of a–f. Dotted lines indicate the SNpc. Scale bars: a–f, 200 μm. (g) Real-time PCR showing mRNA expression of proinflammatory mediators in the SN. Total RNA was isolated from the bilateral SN for real-time PCR 1 day after treatment with vehicle as a control (C); MPTP only (M); MPTP and WIN55,212-2 (MW); MPTP and JWH-133 (MJ); MPTP, WIN55,212-2 and AM630 (MWA); or MPTP, JWH-133 and AM630 (MJA). The CB2 receptor dramatically attenuated MPTP-induced expression of proinflammatory cytokines, including IL-1β, TNF-α and iNOS. The results represent the mean±s.e.m. of three to four separate experiments. ***P<0.001 significantly different from C. #P<0.05 and ##P<0.01, significantly different from M. $P<0.05 and $$P<0.01 significantly different from MW. &P<0.05 and &&P<0.01 significantly different from MJ (ANOVA and Student–Neuman–Keuls analysis).