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

Abstract

Marta Miquel; Rebeca Toledo; Luis I Garcia ; Genaro A Coria-Avila¸ Jorge Manzo. Why should we keep the cerebellum in mind when thinking about addiction?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 activitydependent changes in the efficacy of cerebellar synapses.Revised research involves the cerebellum in drug-induced long-term memory, druginduced 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 re-organization 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.Key words: cerebellum, drug addiction, alcohol, morphine, cocaine, amphetamine, endocannabinoids, sensitization, conditioned emotional memories, cerebellar plasticity 3 THE CEREBELLUM: MORE THAN WHAT WE THOUGHTVery recently, Masao Ito [1] and Narender Ramnani [2] published two excellent and exhaustive reviews on the cerebellum and its functions. Both are highly recommended papers to get a broad perspective on past and current research in this topic. Surely the lesson to be learned from both articles is that later developments in cerebellar research situate functions of the cerebellum beyond motor control. The assumption that the cerebellum controls movement came from medical observations in the mid 19 th and the beginning of the 20 th century [1, 3]. Neurologists observed that lesions in this structure resulted in difficulties in coordinating movement, and experimental physiologists showed that after removing the cerebellum a lack of motor coordination was produced. In the sixties, a specialized role for the cerebellum in the learning of motor patterns was proposed, initially in conventional mo...

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The cerebellum in drug craving

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