Effects of chlordiazepoxide on the emotional reactivity and motor capacities in the cerebellar Lurcher mutant mice

It is now well accepted that besides its roles in motor control, the cerebellum is involved in non-motor functions with emotional aspects. Consistent with this view, several studies highlighted that the cerebellar Lurcher mutant mice (+/Lc), with motor impairments, also exhibited altered emotional reactivity, previously interpreted in term of behavioural disinhibition. In this study, we investigated the effects of a classical anxiolytic on such disinhibition. For that, behaviours of +/Lc and control (+/+) mice injected with NaCl or chlordiazepoxide (CDP 5 and 7.5 mg/kg) were evaluated in the elevated plus-maze test. The motor impact of the drug (7.5 mg/kg only) was also evaluated in the hole-board and unstable platform tests. Our results showed that, compared to the +/+ mice, CDP injection greatly influenced the anxious-related behaviours in the +/Lc mice by reducing their preference to the open areas in the elevated plus-maze test. Furthermore, we found that injection of CDP at the dose of 7.5 mg/kg aggravated motor coordination deficit, altered motor learning capabilities in the mutants and provoked equilibrium disturbances in the non-mutant mice in the unstable platform test. These results indicated that CDP was able to reduce behavioural disinhibition in the cerebellar +/Lc mice and were discussed in term of implication of the cerebellar connections into CDP-sensitive neural circuitries involved in both emotional and motor processes.