Functional role for suppression of the insular–striatal circuit in modulating interoceptive effects of alcohol

Anel A. Jaramillo, Verda E. Agan, Viren H. Makhijani, Stephen Pedroza, Zoe A. McElligott, Joyce Besheer

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular–striatal circuit in modulating behavior under a drug stimulus control.

Original languageEnglish
Pages (from-to)1020-1031
Number of pages12
JournalAddiction Biology
Volume23
Issue number5
DOIs
StatePublished - Sep 2018

Bibliographical note

Publisher Copyright:
© 2017 Society for the Study of Addiction

Keywords

  • accumbens
  • drug discrimination
  • insula

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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