As summarized here, morphological and functional studies in human subjects with compulsive drug abuse indicate that the cerebellum is a prominent participant in addiction. There is increasing evidence that the cerebellum performs functions beyond the sphere of motor control. In this article, we review the evidence involving the cerebellum in addictive behavior. We focus on molecular and cellular targets in the cerebellum, where addictive drugs can act and induce neuroplasticity mechanisms that may contribute to the development of an addictive behavior pattern.
In addition, we analyzed the behavioral consequences of repetitive drug administration that result from activity-dependent changes in the efficacy of cerebellar synapses. The research reviewed includes the cerebellum in drug-induced long-term memory, drug-induced sensitization, and the persevering behavioral phenotype. The results agree on the 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 adaptive changes in receptors, neurotransmitters and intracellular signal transduction pathways that can lead to the reorganization of the cerebellar microzones and, in turn, to functional networks where the cerebellum is located a important nodal structure.
We propose that drug-induced activity-dependent synaptic changes in the cerebellum are crucial for the transition from a pattern of recreational drug use to the compulsive behavioral phenotype. Functional and structural modifications caused by drugs in the cerebellum may increase the susceptibility of frontocerebellar circuits to be changed by repeated exposure to drugs. As part of this functional reorganization, drug-induced cerebellar hyperreactivity appears to be critical in reducing the influence of executive control of the prefrontal cortex on behavior and aiding the transition to an automatic control mode. Addiction involves alterations in the neural mechanisms of plasticity that allow the brain to store information, regenerate and recover from possible disorders or injuries.
In an addicted person, the brain's learning and memory mechanisms that allow them to make decisions and perform acts of will are sick. Addictive drugs force the brain to store harmful data about where, when and how to use the substance. In fact, the drug is the predominant information in the brains of people affected by addiction. Substance use disorders are the result of changes in the brain that can occur with repeated use of alcohol or drugs.
The most serious expression of the disorder, addiction, is associated with changes in the function of the brain circuits involved in pleasure (the reward system), learning, stress, decision-making and self-control. Consequently, the cerebellum is a region of the brain relevant to understanding and designing future treatments for drug addiction. Khodakhah will evaluate whether the cerebellum-VTA pathway can be manipulated, using medications or optogenetics, to treat addiction and prevent relapses after treatment. Other magnetic resonance imaging studies have shown that the cerebellum of people living with an addiction is hyperactive in response to stimuli related to their addiction, such as the image of a syringe.
The role that the cerebellum plays in addiction processes is likely complex and could depend on the particular drug of abuse, the pattern of use, and the stage of the user within the addiction cycle.