Heroin addiction engages negative emotional learning brain circuits in rats
Stephanie A. Carmack, … , Elliot A. Stein, Leandro F. Vendruscolo
Stephanie A. Carmack, … , Elliot A. Stein, Leandro F. Vendruscolo
Published June 3, 2019; First published March 26, 2019
Citation Information: J Clin Invest. 2019;129(6):2480-2484. https://doi.org/10.1172/JCI125534.
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Categories: Concise Communication Neuroscience

Heroin addiction engages negative emotional learning brain circuits in rats

Abstract

Opioid use disorder is associated with the emergence of persistent negative emotional states during drug abstinence that drive compulsive drug taking and seeking. Functional magnetic resonance imaging (fMRI) in rats identified neurocircuits that were activated by stimuli that were previously paired with heroin withdrawal. The activation of amygdala and hypothalamic circuits was related to the degree of heroin dependence, supporting the significance of conditioned negative affect in sustaining compulsive-like heroin seeking and taking and providing neurobiological insights into the drivers of the current opioid crisis.

Authors

Stephanie A. Carmack, Robin J. Keeley, Janaina C. M. Vendruscolo, Emily G. Lowery-Gionta, Hanbing Lu, George F. Koob, Elliot A. Stein, Leandro F. Vendruscolo

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Figure 1

Conditioned heroin withdrawal engages negative emotional learning neurocircuits.

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Conditioned heroin withdrawal engages negative emotional learning neuroc...
(A) Heroin intake during ShA and LgA self-administration sessions. A significant heroin-access × session interaction was observed (F9,171 = 4.25, P = 0.002; 2-way repeated-measures ANOVA). (B) Heroin intake following saline (0 μg/kg, s.c.) or naloxone (Nx) (120 μg/kg, s.c.) treatments during cue pairings, presented as the average of the 4 cue pairings per treatment. Significant main effects of treatment (F1,19 = 35.5, P < 0.0001) and heroin access (F1,19 = 4.215, P = 0.05) were found (2-way repeated-measures ANOVA). (C) Statistical map (F values) of the cue × heroin-access BOLD signal interaction following whole-brain 3-way ANCOVA, with respiration as the covariate (P < 0.01; 233 voxels, corrected for multiple comparisons). The upsampled (to anatomical images) statistical map is superimposed on anatomical coronal images from a representative subject. Below each section is the anterior-posterior distance from bregma (in mm). Data represent mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (different from session 1 and corrected for multiple comparisons in A). n = 11 ShA rats; n = 10 LgA rats.