Cocaine cue-induced dopamine release in the human prefrontal cortex

Area of Science:

• Neuroscience
• Addiction Research
• Neuroimaging

Background:

• Drug-related cues are known to trigger dopamine release in the striatum of individuals with substance use disorders.
• It was previously unknown if these cues also induce dopamine release in the human prefrontal cortex.

Purpose of the Study:

• To investigate whether drug-related cues provoke dopamine release in the human prefrontal cortex of individuals with cocaine dependence.
• To examine the relationship between dopamine release, craving, and receptor availability in cortical and striatal regions.

Main Methods:

• High-resolution positron emission tomography (PET) with [18F]fallypride was used to measure dopamine D2/3 receptor availability.
• Measurements were taken in the presence and absence of cocaine-related cues in individuals with cocaine dependence.
• Binding potential (BPND) was assessed in various brain regions, including the prefrontal cortex and striatum.

Main Results:

• Exposure to cocaine cues significantly decreased [18F]fallypride BPND in the medial orbitofrontal cortex and striatum in participants who reported craving.
• Craving magnitude correlated with BPND changes in multiple prefrontal cortical regions and the striatum.
• Midbrain D2 receptor levels correlated with striatal BPND changes, but not cortical changes, and lower midbrain receptor levels were associated with greater striatal BPND changes and craving.

Conclusions:

• Drug cues induce dopamine release in both cortical and striatal regions in individuals with cocaine use disorder, and this is linked to craving.
• Cortical and subcortical dopamine responses appear to influence drug-seeking behaviors through distinct regulatory mechanisms.
• Midbrain autoreceptors regulate striatal dopamine release but not cortical dopamine release in response to drug cues.