Rimonabant attenuates amphetamine sensitisation in a CCK2 receptor-dependent manner

In this behavioural and pharmacological study in male CCK2 receptor-deficient mice (CCK2−/−), we evaluated the role of the interaction of endocannabinoids (eCBs) and cholecystokinin (CCK) on the regulation of anxiety-related and motor behaviours. Repeated treatment with amphetamine (2 mg/kg daily for four days) induced slightly weaker motor sensitisation in CCK2−/− mice compared to their wild-type (CCK2+/+) littermates. Co-administration of rimonabant (1 mg/kg) with amphetamine antagonised the development of motor sensitisation in CCK2+/+ mice. However, we did not find a similar effect of rimonabant in CCK2−/− mice. We did not find any differences between the behaviour of CCK2+/+ and CCK2−/− mice in models designed to assess emotional behaviours (dark/light exploration, marble burying and conditioned place aversion). This study supports the hypothesis that eCBs play a role in the development of amphetamine-induced sensitisation. Moreover, we have demonstrated that intact CCK2 receptors are necessary for the development of eCB-mediated sensitisation to amphetamine.

► Effect of amphetamine was studied in CCK2 receptor deficient mice.
► Rimonabant abolished amphetamine induced sensitisation in wild-type mice.
► Rimonabant has no effect in CCK2 receptor deficient mice.