Abstract
Smoking is the largest preventable cause of death and disease in the United States. However, <5% of quit attempts are successful, underscoring the urgent need for novel therapeutics. Microglia are one untapped therapeutic target. While previous studies have shown that microglia mediate both inflammatory responses in the brain and brain plasticity, little is known regarding their role in nicotine dependence and withdrawal phenotypes. Here, we examined microglial changes in the striatum—a mesolimbic region implicated in the rewarding effects of drugs and the affective disruptions occurring during withdrawal. We show that both nicotine and withdrawal induce microglial morphological changes; however, proinflammatory effects and anxiogenic behaviors were observed only during nicotine withdrawal. Pharmacological microglial depletion during withdrawal prevented these effects. These results define differential effects of nicotine and withdrawal on inflammatory signaling in the brain, laying the groundwork for development of future smoking cessation therapeutics.
| Original language | English |
|---|---|
| Article number | aax7031 |
| Journal | Science advances |
| Volume | 5 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 9 2019 |
Bibliographical note
Funding Information:This work was supported by the National Institutes of Health–National Institute on Drug Abuse grants DA044311 and DA032681 to J.R.T., grants DA031747 and DA041513 to P.I.O., the NIDA T32 DA016176 (R.D.C.), and a Research Starter Grant from the PhRMA foundation to J.R.T.
Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
ASJC Scopus subject areas
- General