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 language | English |
|---|---|
| Pages (from-to) | 1020-1031 |
| Number of pages | 12 |
| Journal | Addiction Biology |
| Volume | 23 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 2018 |
Bibliographical note
Publisher Copyright:© 2017 Society for the Study of Addiction
Funding
The authors would like to thank Dr Thomas Kash for helpful discussions regarding the utilization of DREADDs, Dr Michael Chua for assisting in the training and use of fluorescent microscopy and the NIDA Drug Supply Program for providing the CNO. This work was supported, in part, by grant AA019682 to JB from the National Institute on Alcohol Abuse and Alcoholism and by the Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill and grant AA011605. AAJ was supported, in part, by an National Science Foundation Graduate Research Fellowship DGE-1144081 and then by F31AA024973 while working on data collection and the writing of this manuscript. VHM was supported by T32 NS007431. The authors declare no conflict of interest. AAJ and JB were responsible for the study concept and design. AAJ, VEA, VHM and SP contributed to the acquisition of the animal data. ZAM conducted the electrophysiological experiments. AAJ and JB conducted data analysis and interpretation of findings. AAJ drafted the article. AAJ and JB provided critical revision of the article for important intellectual content. All authors critically reviewed content and approved the final version for publication.
| Funders | Funder number |
|---|---|
| Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse | |
| U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China | F31AA024973, 1144081, T32 NS007431 |
| National Institute on Alcohol Abuse and Alcoholism | K01AA023555, F31AA024973, P50AA011605, R01AA019682 |
| Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill | AA011605 |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | T32NS007431 |
Keywords
- accumbens
- drug discrimination
- insula
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology
- Psychiatry and Mental health
