Stimulant-induced dopamine increases are markedly blunted in active cocaine abusers

Area of Science:

• Neuroscience
• Addiction Research
• Psychopharmacology

Background:

• Dopamine signaling in the nucleus accumbens is crucial for experiencing cocaine reward.
• Previous studies indicated reduced dopamine increases in the striatum of detoxified cocaine abusers.
• The reasons for this blunted dopamine response remain unclear, with possibilities including detoxification effects or lack of drug cues.

Purpose of the Study:

• To investigate whether blunted dopamine responses in cocaine abusers are due to detoxification or the absence of cocaine cues during stimulant exposure.
• To measure dopamine increases induced by methylphenidate in non-detoxified cocaine abusers and controls.

Main Methods:

• Positron emission tomography (PET) with [(11)C]raclopride was used to measure dopamine increases.
• 62 participants (43 non-detoxified cocaine abusers, 19 controls) received intravenous methylphenidate.
• In a subset of abusers, dopamine increases were compared with and without cocaine cue-videos.

Main Results:

• Methylphenidate significantly increased dopamine in the dorsal and ventral striatum of controls.
• In cocaine abusers, methylphenidate did not elicit dopamine increases compared to placebo, irrespective of cocaine cues.
• Despite attenuated dopamine release, methylphenidate-induced changes in the ventral striatum correlated with intense drug craving in abusers.

Conclusions:

• Active cocaine abusers exhibit markedly reduced dopamine signaling through D2 receptors, even without drug cues.
• This attenuated dopaminergic response may contribute to the compulsive nature of cocaine use.
• Findings suggest that reduced D2 receptor signaling is a characteristic of active cocaine abuse, not solely a result of detoxification.