Scientists identify brain circuits engaged in compulsive heroin use

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Rat brain image showing hypothalamic and amygdala nuclei associated with conditioned heroin withdrawal.
Courtesy of Integrative Neuroscience and Neuroimaging Research Branches, NIDA, IRP
Rat brain image showing hypothalamic and amygdala nuclei associated with conditioned heroin withdrawal.

People addicted to heroin and other opioids experience withdrawal when they discontinue or no longer have access to these drugs. Withdrawal can include a host of negative emotional symptoms such as depression, anxiety, pain, and dysphoria, which can drive people to use opioids again in order to relieve those symptoms. Environmental stimuli that people have come to associate with withdrawal and the negative emotional state that accompanies it (i.e., conditioned cues) can themselves trigger withdrawal and may perpetuate drug use.

Scientists at NIDA’s Intramural Research Program (IRP) wanted to learn more about the brain circuits that enable these conditioned withdrawal cues to promote compulsive heroin use. Using fMRI, they scanned the brains of heroin-dependent rats while the animals were presented with a specific odor (i.e., the conditioned cue) that they had previously come to associate with the drug withdrawal. They found that in addition to triggering heroin seeking and taking, these cues engaged the hypothalamus and amygdala nuclei, brain systems involved in negative emotional learning.

Overall, this study provides an innovative conceptual framework for understanding opioid use disorder (OUD). Current Food and Drug Administration-approved medications for OUD targeting opioid receptors can be effective but may not fully alleviate cue-conditioned withdrawal. This study provides insight into the brain circuits engaged during this process and could lead to pharmacological or behavioral interventions to reduce relapse and overdose. These findings also underscore the need for additional research aimed toward understanding the neurobiology of negative emotional learning in addiction. These efforts are currently underway at NIDA IRP.