Translational approach to apathy-like behavior in mice: From the practical point of view

Psychiatry Clin Neurosci. 2019 Nov;73(11):685-689. doi: 10.1111/pcn.12915. Epub 2019 Aug 22.


Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre-clinical levels. To study apathy-like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal-directed behaviors. We recently found that the chronic loss of function of a specific cell type (striatal dopamine receptor type 2-expressing medium spiny neurons, D2-MSN) in a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy-like behavior in a food-seeking operant task. We further showed that VLS D2-MSN are activated at the preparatory period, and that optogenetic inhibition of VLS D2-MSN during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2-MSN mediate apathy-like behavior in mice. Mice bearing VLS D2-MSN dysfunction can thus be regarded as an apathy model for future translational studies.

Keywords: fiberphotometry; goal-directed behavior; motivation; operant conditioning; optogenetics.

Publication types

  • Review

MeSH terms

  • Animals
  • Apathy*
  • Behavior, Animal*
  • Behavioral Research / methods*
  • Mice
  • Optogenetics
  • Translational Medical Research