Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [11C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.
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The recruitment and psychological screening were carried out at the Harbor University of California—Los Angeles Medical Center and Veteran Administration Medical Center at Portland, Oregon. We thank David Schlyer and Michael Schueller for performing cyclotron operations; Donald Warner, David Alexoff and Paul Vaska for performing PET operations; Richard Ferrieri, Colleen Shea, Youwen Xu, Lisa Muench and Payton King for radiotracer preparation and analysis, Karen Apelskog-Torres for study protocol preparation, and Barbara Hubbard and Pauline Carter for patient care.
The PET study was carried out at the Brookhaven National Laboratory with infrastructure support from the US Department of Energy OBER (DE-ACO2-76CH00016) and under support in part by NIH: R01DA06891 (Dr Wang), MO1RR10710 (the General Clinical Research Center of Stony Brook University) and Z01AA000550 (Dr Volkow). The authors declare no conflict of interest.
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Wang, G., Smith, L., Volkow, N. et al. Decreased dopamine activity predicts relapse in methamphetamine abusers. Mol Psychiatry 17, 918–925 (2012). https://doi.org/10.1038/mp.2011.86
- dopamine release
- early withdrawal
- positron emission tomography
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