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 March 26, 2019
Citation Information: J Clin Invest. 2019;129(6):2480-2484. https://doi.org/10.1172/JCI125534.
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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 2

Withdrawal severity during conditioning is associated with changes in the hypothalamic and amygdala nuclei BOLD signal in response to the naloxone-paired cue.

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Withdrawal severity during conditioning is associated with changes in th...
(A) Hypothalamic cluster extracted from the BOLD signal cue × heroin-access interaction shown in Figure 1C, with a 3D rendered whole-brain underlay. A, anterior; P, posterior. (B) Mean percentage of BOLD signal change from baseline in the hypothalamic cluster to the cue-only presentations. Dot plot displays individual data for each condition. Sal, saline. (C) Scatter plot of heroin intake during naloxone conditioning and BOLD signal response in the hypothalamic cluster to the naloxone-paired cue across both heroin-access groups (Pearson’s correlation). (D) Amygdala nuclei extracted from the BOLD signal cue × heroin-access interaction shown in Figure 1C, with a 3D rendered whole-brain underlay. (E) Mean percentage of BOLD signal change from baseline in amygdala nuclei to the cue-only presentations. Dot plot displays individual data for each condition. (F) Scatter plot of heroin intake during naloxone conditioning and BOLD signal response in the amygdala nuclei to the naloxone-paired cue across both heroin-access groups (Pearson’s correlation). n = 11 ShA rats; n = 10 LgA rats.