The Cerebellum on Cocaine

Abstract

The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement in executive and emotional functions in the last decades. First in 2009 and then, in 2016, we raised why we should consider the cerebellum when thinking about drug addiction. A decade later, mounting evidence strongly suggests the cerebellar involvement in this disorder. Nevertheless, direct evidence is still partial and related mainly to drug-induced reward memory, but recent results about cerebellar functions may provide new insights into its role in addiction. The present review does not intend to be a compelling revision on available findings, as we did in the two previous reviews. This minireview focuses on specific findings of the cerebellum's role in drug-related reward memories and the way ahead for future research. The results discussed here provide grounds for involving the cerebellar cortex's apical region in regulating behavior driven by drug-cue associations. They also suggest that the cerebellar cortex dysfunction may facilitate drug-induced learning by increasing glutamatergic output from the deep cerebellar nucleus (DCN) to the ventral tegmental area (VTA) and neural activity in its projecting areas.

TMEM106B deficiency impairs cerebellar myelination and synaptic integrity with Purkinje cell loss

“…These results strongly support that TMEM106B is closely linked to cerebellar functions. Accumulating evidence supports that the cerebellum plays critical roles in cognition, executive functions [ 1 ], emotion processing [ 18 ], reward memory, and addiction [ 28 ], in addition to its traditionally recognized function in motor coordination and control. In addition, cerebellar dysfunction has been recently tightly associated with FTLD and other neurodegenerative diseases [ 2 , 3 , 7 , 8 , 43 ].…”

Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications

“…Finally, electrophysiological, pharmacological and immunohistochemical research studies investigated how different neurotransmitter systems, such as noradrenergic, cholinergic or dopaminergic system, can modulate the synaptic transmission and thereby influence the functional output through activation of specific cerebellar receptor subtypes (156)(157)(158)(159)(160)(161)(162)(163)(164)(165)(166).…”

“…Concerning the dopaminergic system, the cerebellum was traditionally not considered an elective dopaminergic region. However, lesion studies have shown the involvement of cerebellum in dopamine deficit-related neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia, autism spectrum disorders, and drug addiction (158)(159)(160)(161). Moreover, data coming from invasive studies in animal and tractography observation in humans revealed relevant patterns of intracerebellar dopaminergic connectivity, such as between the DN and the cerebellar cortex, and extrinsic interconnections between the cerebellum and traditional dopaminergic areas of the brain, including the midbrain, the neostriatum, the neocortex (162)(163)(164)(165).…”

Identifying Internet Addiction and Evaluating the Efficacy of Treatment Based on Functional Connectivity Density: A Machine Learning Study

“…The cerebellum, traditionally considered a pure motor center, is now concerned for its various cognitive functions, including habit formation. The cerebellum is involved in rapid and automatic behavioral responses in substance dependence, accounting for the habitual and compulsive drug abuse (Miquel et al, 2019(Miquel et al, , 2020. In IA studies, increased activations in the cerebellum were also found in individuals with IA when exposed to internet cues, implicating automatic habitual reactions to internet (Schmitgen et al, 2020).…”