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 (2mg/kg daily for four days) induced slightly weaker motor sensitisation in CCK2(-/-) mice compared to their wild-type (CCK2(+/+)) littermates. Co-administration of rimonabant (1mg/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.