Role of mPFC and nucleus accumbens circuitry in modulation of a nicotine plus alcohol compound drug state

Patrick A. Randall, Zoe A. McElligott, Joyce Besheer

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Combined use of nicotine and alcohol constitute a significant public health risk. An important aspect of drug use and dependence are the various cues, both external (contextual) and internal (interoceptive) that influence drug-seeking and drug-taking behavior. The present experiments employed the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and complementary Pavlovian drug discrimination procedures (feature-positive and feature-negative training conditions) in order to examine whether medial prefrontal cortex (prelimbic; mPFC-PL) projections to the nucleus accumbens core (AcbC) modulate sensitivity to a nicotine + alcohol (N + A) interoceptive cue. First, we show neuronal activation in mPFC-PL and AcbC following treatment with N + A. Next, we demonstrate that chemogenetic silencing of projections from mPFC-PL to nucleus accumbens core decrease sensitivity to the N + A interoceptive cue, while enhancing sensitivity to the individual components, suggesting an important role for this specific projection. Furthermore, we demonstrate that clozapine-N-oxide (CNO), the ligand used to activate the DREADDs, had no effect in parallel mCherry controls. These findings contribute important information regarding our understanding of the cortical-striatal circuitry that regulates sensitivity to the interoceptive effects of a compound N + A cue.

Original languageEnglish (US)
Article numbere12782
JournalAddiction Biology
Issue number4
StatePublished - Jul 1 2020

All Science Journal Classification (ASJC) codes

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


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