The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management

Marco Venniro, Daniele Caprioli, Michelle Zhang, Leslie R. Whitaker, Shiliang Zhang, Brandon L. Warren, Carlo Cifani, Nathan J. Marchant, Ofer Yizhar, Jennifer M. Bossert, Cristiano Chiamulera, Marisela Morales, Yavin Shaham

Research output: Contribution to JournalArticleAcademicpeer-review

91 Citations (Scopus)


Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug reward to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and, until recently, an animal model of this human condition did not exist. Here we used a novel rat model, in which the availability of a mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration, to demonstrate that the activation of monosynaptic glutamatergic projections from anterior insular cortex to central amygdala is critical to relapse after the cessation of contingency management. We identified the anterior insular cortex-to-central amygdala projection as a new addiction- and motivation-related projection and a potential target for relapse prevention.

Original languageEnglish
Pages (from-to)414-427
Number of pages14
Issue number2
Publication statusPublished - 11 Oct 2017


  • CNO
  • amygdala
  • choice
  • contingency management
  • dopamine receptor
  • insular cortex
  • methamphetamine
  • relapse
  • retrograde tracing

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