The role of the cerebellum in drug-cue associative memory: functional interactions with the medial prefrontal cortex

Eur J Neurosci. 2019 Aug;50(3):2613-2622. doi: 10.1111/ejn.14187. Epub 2018 Oct 24.


Drug-induced Pavlovian memories are thought to be crucial for drug addiction because they guide behaviour towards environments with drug availability. Drug-related memory depends on persistent changes in dopamine-glutamate interactions in the medial prefrontal cortex (mPFC), basolateral amygdala, nucleus accumbens core and hippocampus. Recent evidence from our laboratory indicated that the cerebellum is also a relevant node for drug-cue associations. In the present study, we tested the role that specific regions of the cerebellum and mPFC play in the acquisition of cocaine-induced preference conditioning. Quinolinic acid was used to manage a permanent deactivation of lobule VIII in the vermis prior to conditioning. Additionally, lidocaine was infused into the prelimbic and infralimbic (IL) cortices for reversible deactivation before every training session. The present findings show, for the first time, that the cerebellum and mPFC might act together in order to acquire drug-cue Pavlovian associations. Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine-induced preference conditioning. Moreover, simultaneous IL-cerebellar deactivation prevented the effect of either of the separate deactivations. Therefore, similar to the IL cortex, neural activity in the cerebellum may be crucial for ensuring inhibitory control of the expression of cocaine-related memories.

Keywords: cocaine; drug-induced conditioning; lidocaine; odours; quinolinic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology*
  • Cerebellum / drug effects
  • Cerebellum / physiology*
  • Cocaine / administration & dosage*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Cues*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Injections, Intraventricular
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley


  • Dopamine Uptake Inhibitors
  • Cocaine