Addiction and the cerebellum with a focus on actions of opioid receptors

Neurosci Biobehav Rev. 2021 Dec:131:229-247. doi: 10.1016/j.neubiorev.2021.09.021. Epub 2021 Sep 20.


Increasing evidence suggests that the cerebellum could play a role in the higher cognitive processes involved in addiction as the cerebellum contains anatomical and functional pathways to circuitry controlling motivation and saliency. In addition, the cerebellum exhibits a widespread presence of receptors, including opioid receptors which are known to play a prominent role in synaptic and circuit mechanisms of plasticity associated with drug use and development of addiction to opioids and other drugs of abuse. Further, the presence of perineural nets (PNNs) in the cerebellum which contain proteins known to alter synaptic plasticity could contribute to addiction. The role the cerebellum plays in processes of addiction 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. In this review, we discuss functional and structural modifications shown to be produced in the cerebellum by opioids that exhibit dependency-inducing properties which provide support for the conclusion that the cerebellum plays a role in addiction.

Keywords: Addiction; Cerebellum; Endogenous opioid; Learning; Opioid receptor; Perineural nets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Behavior, Addictive*
  • Cerebellum
  • Humans
  • Neuronal Plasticity / physiology
  • Receptors, Opioid
  • Substance-Related Disorders*


  • Analgesics, Opioid
  • Receptors, Opioid