Methylphenidate attenuates brain metabolic activation patterns induced by cocaine cues in cocaine abusers

Objectives Dopamine is implicated in conditioned responses to drugs of abuse. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine increases triggered by conditioned-cues.

Methods The effects of increasing tonic dopamine levels with oral methylphenidate on the regional brain metabolic activation induced by cocaine-cues were measured with PET and FDG in 24 active cocaine abusers tested four times; twice watching a neutral video (nature scenes) and twice watching a cocaine-cues video with each video preceded once by placebo and once by methylphenidate (20 mg, po).

Results The cocaine-cues video significantly increased self-reports of craving to the same extent when preceded by placebo (68%) or methylphenidate (64%). In contrast, SPM analysis of the normalized metabolic images (comparison of neutral vs cocaine-cues videos) showed greater differences with placebo than with methylphenidate; with placebo there were significant decreases with the cocaine-cues (p <0.005) in left limbic regions including posterior insula (6%), lateral posterior orbitofrontal (5%), accumbens (7%) and in right parahippocampal gyrus (6%), whereas with methylphenidate there were only decreases in auditory (BA 22 and 42) and visual areas (inferior BA 18), which also occurred with placebo. None of these metabolic changes were associated with craving.

Conclusions These results corroborate our hypothesis of a blunting of regional brain metabolic responses to cocaine-cues by oral methylphenidate but failed to corroborate a parallel blunting in craving. Future studies that evaluate the functional significance of the blunting of limbic responses to conditioned-cues by a low dose of oral methylphenidate may help identify potential therapeutic benefits of this medication in cocaine addiction.

Research Support NIH and Department of Energ