Dopamine signaling in the dorsomedial striatum promotes compulsive behavior

Jillian L. Seiler, Caitlin V. Cosme, Venus N. Sherathiya, Michael D. Schaid, Joseph M. Bianco, Abigael S. Bridgemohan, Talia N. Lerner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Compulsive behavior is a defining feature of disorders such as substance use disorders. Current evidence suggests that corticostriatal circuits control the expression of established compulsions, but little is known about the mechanisms regulating the development of compulsions. We hypothesized that dopamine, a critical modulator of striatal synaptic plasticity, could control alterations in corticostriatal circuits leading to the development of compulsions (defined here as continued reward seeking in the face of punishment). We used dual-site fiber photometry to measure dopamine axon activity in the dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) as compulsions emerged. Individual variability in the speed with which compulsions emerged was predicted by DMS dopamine axon activity. Amplifying this dopamine signal accelerated animals’ transitions to compulsion, whereas inhibition delayed it. In contrast, amplifying DLS dopamine signaling had no effect on the emergence of compulsions. These results establish DMS dopamine signaling as a key controller of the development of compulsive reward seeking.

Original languageEnglish (US)
Pages (from-to)1175-1188.e5
JournalCurrent Biology
Issue number5
StatePublished - Mar 14 2022


  • compulsive behavior
  • dopamine
  • dorsal striatum
  • fiber photometry
  • habit formation
  • optogenetics
  • punishment-resistant reward seeking
  • reward learning
  • substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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