Effects of Naltrexone on Large-Scale Network Interactions in Methamphetamine Use Disorder

Frontiers in Psychiatry

Angelica M. Morales¹  William F. Hoffman³  Milky Kohno⁴  Holly McCready⁵  Laura E. Dennis⁵  P. Todd Korthuis⁶ 

[1] Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States;Department of Psychiatry, Oregon Health and Science University, Portland, OR, United States;Mental Health Division, Veterans Affairs Portland Health Care System, Portland, OR, United States;Methamphetamine Abuse Research Center, Oregon Health and Science University and Veterans Affairs Portland Health Care System, Portland, OR, United States;Research and Development Service, Veterans Affairs Portland Health Care System, Portland, OR, United States;Section of Addiction Medicine, Oregon Health and Science University, Portland, OR, United States;

关键词: naltrexone;    resting-state functional magnetic resonance imaging;    methamphetamine;    striatum;    functional connectivity;   

DOI  :  10.3389/fpsyt.2019.00603

来源: DOAJ

【 摘 要 】

Naltrexone attenuates craving, and the subjective effects of methamphetamine and extended-release naltrexone (XR-NTX) reduces functional connectivity between regions of the striatum and limbic cortex. Naltrexone modulates neural activity at dopaminergic synapses; however, it is unclear whether naltrexone has an effect on large-scale brain networks. Functional networks interact to coordinate behavior, and as substance-use disorders are associated with an imbalance between reward and cognitive control networks, treatment approaches that target interactive brain systems underlying addiction may be a useful adjunct for behavioral therapies. The objective of this study was to examine the effect of XR-NTX on large-scale brain networks and to determine whether changes in network relationships attenuate drug use, craving, and addiction severity. Thirty-nine participants in or seeking treatment for methamphetamine-use disorder were enrolled in a clinical trial of XR-NTX between May 2013 and March 2015 (Clinicaltrials.gov NCT01822132). Functional magnetic resonance imaging (fMRI) and questionnaires were conducted before and after double-blinded randomization to a 4-week injection of XR-NTX or placebo. In the XR-NTX group, methamphetamine use was reduced along with a decrease in the coupling between executive control (ECN) and default mode (DMN) networks. As decoupling of ECN and DMN networks was associated with change in the severity of dependence, the results suggest that XR-NTX may modulate and enhance ECN attentional resources and suppress DMN self-referential and emotional processing. This study identifies the effect of naltrexone on changes in the intrinsic functional coupling of large-scale brain networks and provides a more systematic understanding of how large-scale networks interact to promote behavioral change in methamphetamine-use disorder.

【 授权许可】

Unknown