Imaging norepinephrine transporter in abstinent cocaine users using (S,S)-[11C]O-methylreboxetine

Objectives Although norepinephrine transporter (NET) receptor function has been demonstrated to be increased during cocaine dependence[1], how it adapts during early and late abstinence has not been well characterized. The aim of this study was to examine changes in NET availability in early (1 week) and late (3+ weeks) abstinence from cocaine dependence.

Methods Twelve healthy subjects (38 ±11 y) and fifteen subjects with 22 ± 7 years of cocaine use (43 ± 6 y) were studied with (S,S)-[11C]O-methylreboxetine ([11C]MRB) using the High Resolution Research Tomograph (HRRT). Individuals with cocaine dependence were admitted to an in-patient unit with PET scanning performed over a period of 3 to 38 days of abstinence. The regional brain NET binding potential (BPND) was estimated by the Multiple Reference Tissue Model 2 (MRTM2) with the occipital cortex as a reference region. ROI values were obtained with the AAL template registered to individual MR scans.

Results Compared with controls, subjects with cocaine dependence had higher BPND values (70 %; p<0.05) after 1 week of abstinence in the ventral lateral thalamus and that remained elevated (85 %; p<0.01) during the 2nd week of abstinence. By the 3rd week, NET levels declined to controls levels (11 %; p=0.60). Further, similar significant patterns were observed in the measurement of the whole thalamus, pulvinar, and the midbrain raphe nuclei.

Conclusions This study suggests that NET is increased in the thalamus during early abstinence from chronic cocaine use, which is consistent with our previous finding[1]. The results of NET binding potential evolving during recovery suggest an important neural correlate of the changes of craving and self-control during the first few weeks of abstinence. [1]Ding YS. 2010. Synapse. 64:30-38

Research Support Funded by NIH R21DA026998 (Li) and 5T32DA022975-04 (Lee)