Dopaminergic response to drug words in cocaine addiction

Abstract

When exposed to drug conditioned cues (stimuli associated with the drug), addicted individuals experience an intense desire for the drug, which is associated with increased dopamine cell firing. We hypothesized that drug-related words can trigger activation in the mesencephalon, where dopaminergic cells are located. During functional magnetic resonance imaging (fMRI), 15 individuals with cocaine use disorders and 15 demographically matched healthy control subjects pressed buttons for color of drug-related versus neutral words. Results showed that the drug words, but not neutral words, activated the mesencephalon in the cocaine users only. Further, in the cocaine users only, these increased drug-related mesencephalic responses were associated with enhanced verbal fluency specifically for drug words. Our results for the first time demonstrate fMRI response to drug words in cocaine-addicted individuals in mesencephalic regions as possibly associated with dopaminergic mechanisms and with conditioning to language (in this case drug words). The correlation between the brief verbal fluency test, which can be easily administered (crucial for clinical studies), and fMRI cue reactivity could be used as a biomarker of neurobiological changes in addiction.

Figure 1.

Behavioral and neuroimaging results. A, Drug and neutral 1 min verbal fluency in 15 cocaine-addicted and 15 matched healthy control participants. Variables are unstandardized residuals obtained after the effects of verbal IQ on correct word fluency responses were removed (with regression analyses). B, Drug and neutral word mesencephalon responses in all study subjects. Variables are percentage change in the BOLD signal (from a fixation baseline) in the right mesencephalon (x = 3, y = −15, z = −12) as a function of type of word. C, Correlation between percentage change in the BOLD signal (differential response to drug > neutral words) in the left mesencephalon (x = −6, y = −15, z = −18) with the respective verbal fluency change (corrected for verbal IQ) across all study subjects. Error bars represent SEM. Midsagittal and axial maps on the right show the mesencephalon activated to drug > neutral words in the cocaine-addicted participants. *p < 0.05; ^†p < 0.01.