Chemogenetic manipulations of ventral tegmental area dopamine neurons reveal multifaceted roles in cocaine abuse

Stephen V. Mahler, Zachary D. Brodnik, Brittney M. Cox, William C. Buchta, Brandon S. Bentzley, Julian Quintanilla, Zackary A. Cope, Edwin C. Lin, Matthew D. Riedy, Michael D. Scofield, Justin Messinger, Christina M. Ruiz, Arthur C. Riegel, Rodrigo A. España, Gary Aston-Jones

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of G q signaling, but not G s signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions. In contrast, engaging inhibitory G i/o signaling in DA neurons blunted the reinforcing and priming effects of cocaine, reduced stress-potentiated reinstatement, and altered behavioral strategies for cocaine seeking and taking. Results demonstrate that DA neurons play several distinct roles in cocaine seeking, depending on behavioral context, G-protein-signaling cascades, and DA neuron efferent targets, highlighting their multifaceted roles in addiction.

Original languageEnglish (US)
Pages (from-to)503-518
Number of pages16
JournalJournal of Neuroscience
Issue number3
StatePublished - Jan 16 2019
Externally publishedYes


  • Addiction
  • Conditioned cues
  • Motivation
  • Neural circuits
  • Reinstatement

ASJC Scopus subject areas

  • General Neuroscience


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