Smoking-Induced Dopamine Release Studied with [11C]Raclopride PET

Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon; Ryu, Hye Jung; Lee, Eun Ju; Ryu, Chang Hung; Jeong, In Soon; Hong, Soo Kyung; Lee, Jae Sung; Seo, Hong Gwan; Jeong, Jae Min; Lee, Won Woo; Kim, Sang Eun

Abstract

PURPOSE
It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [11C]raclopride. MATERIALS AND METHODS: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4+/-1.7 years) were enrolled in this study. [11C]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus- constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar) /cerebellar activity, was measured under equilibrium condition at baseline and smoking session. RESULTS: The mean decrease in binding potential of [11C]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7 %, 4.0 % and 7.8 %, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). CONCLUSION: These data demonstrate that in vivo imaging with [11C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.