Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

PLoS One

Jean Logan¹  Joanna S. Fowler¹  Frank Telang¹  Gene-Jack Wang¹  Kith Pradhan²  Dardo Tomasi²  Rita Z. Goldstein²  Christopher Wong²  Millard Jayne²  Nelly Alia-Klein²  Nora D. Volkow³ 

[1] Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States of America;Medical Department, Brookhaven National Laboratory, Upton, New York, United States of America;National Institute on Drug Abuse, Bethesda, Maryland, United States of America

关键词: Cocaine;    Drug metabolism;    Drug interactions;    Glucose metabolism;    Functional magnetic resonance imaging;    Amygdala;    Conditioned response;    Heart rate;   

DOI  :  10.1371/journal.pone.0011509

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Dopamine (phasic release) is implicated in conditioned responses. 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 release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.

【 授权许可】

CC BY