The Cerebellar Landscape of Drug Addiction

It is well known that addictive drugs induce long-lasting molecular and structural plasticity changes in cortico-striatal-limbic circuits. Notwithstanding the accumulating evidence, drug-induced cerebellar plasticity is an unexplored field and has not been considered to be as relevant as basal ganglia networks in the explanation of drug addiction. In this chapter, we aim at discussing several recent findings that support the involvement of the cerebellum in some of those brain functions altered in the addicted brain. All drugs with an addictive potential have been shown to cause/produce sensitization of their stimulating and incentive effects. Importantly, drug-dependent sensitization is accompanied by long-lasting changes in the cerebellum that appear to be incubated during the withdrawal periods. Stable plastic alterations in striatum-cortico-limbic circuits underlie the permanence and capability of drug-related conditioned memories to induce relapse. Of note, cerebellar activations have been consistently described during the exposure to drug-associated cues. Moreover, we have found as a particular and distinctive factor higher levels of cFOS expression in the dorsal region of the granule cell layer. Finally, it appears that in addicts where there is no flexible behavioral executive control, the cerebellum might hijack those functions usually performed by the prefrontal cortex.