Why Should We Keep the Cerebellum in Mind When Thinking About Addiction?

Marta      Miquel; Rebeca      Toledo; Luis   I.   Garcia; Genaro   A.   Coria-Avila; Jorge      Manzo

Abstract

Increasing evidence has involved the cerebellum in functions beyond the sphere of motor control. In the present article, we review evidence that involves the cerebellum in addictive behaviour. We aimed on molecular and cellular targets in the cerebellum where addictive drugs can act and induce mechanisms of neuroplasticity that may contribute to the development of an addictive pattern of behaviour. Also, we analyzed the behavioural consequences of repetitive drug administration that result from activity-dependent changes in the efficacy of cerebellar synapses. Revised research involves the cerebellum in drug-induced long-term memory, drug-induced sensitization and the perseverative behavioural phenotype. Results agree to relevant participation of the cerebellum in the functional systems underlying drug addiction. The molecular and cellular actions of addictive drugs in the cerebellum involve long-term adaptative changes in receptors, neurotransmitters and intracellular signalling transduction pathways that may lead to the reorganization of cerebellar microzones and in turn to functional networks where the cerebellum is an important nodal structure. We propose that drug induced activity-dependent synaptic changes in the cerebellum are crucial to the transition from a pattern of recreational drug taking to the compulsive behavioural phenotype. Functional and structural modifications produced by drugs in the cerebellum may enhance the susceptibility of fronto-cerebellar circuitry to be changed by repeated drug exposure. As a part of this functional reorganization, drug-induced cerebellar hyper-responsiveness appears to be central to reducing the influence of executive control of the prefrontal cortex on behaviour and aiding the transition to an automatic mode of control.

Keywords: Cerebellum, drug addiction, alcohol, morphine, cocaine, amphetamine, endocannabinoids, sensitization, conditioned emotional memories, cerebellar plasticity