期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 18, 页码 9066-9071出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1819978116
关键词
methamphetamine self-administration; compulsive behavior; frontostriatal functional circuits; functional connectivity; foot shock punishment
资金
- Intramural Research Program of the National Institute on Drug Abuse
- NATIONAL INSTITUTE ON DRUG ABUSE [ZIADA000572, ZIADA000597] Funding Source: NIH RePORTER
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.
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