Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals

Balance of the “go” and “stop” circuits is disrupted in rats taking drug compulsively. (Image courtesy of Dr. Yuzheng Hu)

Hot Off the Press – May 6, 2019.

We report that in a methamphetamine self-administration experiment, all rats show changes in the balance between “go” and “stop” brain circuits, however after foot shock punishment, behavior in the addictive subgroup is strongly correlated with the change in the balance of “go” and “stop” circuits, while the balance returns towards normal in rats that reduce use after it is paired with punishment, suggesting that non-invasive brain stimulation targeting these circuits in addicts may help restore the go-stop balance and allow individuals to control their drug use.

Publication Information

Hu, Yuzheng; Salmeron, Betty Jo; Krasnova, Irina N; Gu, Hong; Lu, Hanbing; Bonci, Antonello; Cadet, Jean L; Stein, Elliot A; Yang, Yihong

Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals. Journal Article

In: Proc Natl Acad Sci U S A, vol. 116, no. 18, pp. 9066–9071, 2019, ISSN: 1091-6490 (Electronic); 0027-8424 (Linking).

Abstract | Links

@article{Hu:2019aa,

title = {Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals.},

author = {Yuzheng Hu and Betty Jo Salmeron and Irina N Krasnova and Hong Gu and Hanbing Lu and Antonello Bonci and Jean L Cadet and Elliot A Stein and Yihong Yang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30988198},

doi = {10.1073/pnas.1819978116},

issn = {1091-6490 (Electronic); 0027-8424 (Linking)},

year  = {2019},

date = {2019-04-30},

urldate = {2019-04-30},

journal = {Proc Natl Acad Sci U S A},

volume = {116},

number = {18},

pages = {9066--9071},

address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Programs, National Institutes of Health, Baltimore, MD 21224; yihongyang@intra.nida.nih.gov huyuzheng@zju.edu.cn.},

abstract = {Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}