Fig. 3

Treatment with rimonabant rescues the spatial memory deficits in RTT mice. Mecp2-308 heterozygous female (RTT) mice and wild-type (Wt) controls received intraperitoneal daily injections with the CB1 cannabinoid receptor inverse agonist rimonabant (Rim, 0.3 mg/kg) or vehicle for 7 days. Behavioral testing was performed to assess drug effects on the cognitive impairments typically displayed by RTT mice at a symptomatic stage: on the 6th day of treatment mice underwent the object location test to assess memory of spatial configurations; on the 7th day spatial short-term memory was assessed using the Y-maze test. Both tests are based on the spontaneous tendency of rodents to explore novel stimuli (displaced object or unexplored arm of the maze). The preference index (time exploring the novel/(familiar + novel) objects/arms) was calculated and considered a measure of spatial memory retention and novelty discrimination. (A) Treatment with Rim restores the ability of RTT mice to discriminate spatial novelty in both the object location and (B) Y-maze tests. The dashed line represents the chance levels (50% in A; 33% in B). N = 5–8. Data are mean ± SEM. ^$p < 0.05, ^$$ p < 0.01 (one sample Student’s t-test versus chance level)