PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users Jie Shi a , Li-Yan Zhao a , Marc L. Copersino b , Yu-Xia Fang c , Yingmao Chen d , Jiahe Tian d , Yanping Deng a , Yinliang Shuai e , Jun Jin e , Lin Lu a, ⁎ a National Institute on Drug Dependence, Peking University, Beijing 100083, China b Harvard Medical School, McLean Hospital, Alcohol and Drug Abuse Treatment Program, Belmont, MA 02478, USA c Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA d China PLA General Hospital, Beijing 100062, China e Beijing Ankang Hospital, Beijing 102406, China Received 23 March 2007; received in revised form 23 September 2007; accepted 27 September 2007 Available online 10 October 2007 Abstract It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum (caudate and putamen), and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment. Binding of [ 11 C]–2β–carbomethoxy–3β–aryltropane ([ 11 C] CFT) as a brain dopamine transporter ligand was measured with positron emission tomography (PET) in eleven former heroin users with prolonged abstinence, ten patients receiving methadone maintenance treatment and ten healthy control subjects. Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined. In comparison with healthy control subjects, methadone maintenance treatment subjects had lower DAT uptake function in the bilateral caudate and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral caudate. Moreover, in comparison to the prolonged abstinence subjects, the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen. DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects; however, DAT uptake function in the bilateral caudate was significantly correlated with subjective anxiety in methadone maintenance treatment subjects. Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment, and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain. © 2007 Elsevier B.V. All rights reserved. Keywords: Heroin abuse; Craving; Anxiety; Prolonged withdrawal; Dopamine transporter; Positron emission tomography; Methadone maintenance treatment 1. Introduction Opioid abuse is a significant global public health problem. Almost 16 million people worldwide are abusers of opioids, of which about 70% (11 million) are abusers of heroin (diace- tylmorphine) (UNODC, 2006). Methadone maintenance treat- ment has been demonstrated to be effective in reducing or eliminating opioid drug use (Dole and Nyswander, 1965; Dole et al., 1966; Strain et al., 1999) and reducing heroin craving (Greenwald, 2002; Leri et al., 2004), and it is the most commonly prescribed opioid agonist therapy for the treatment of heroin dependence. Methadone hydrochloride is a synthetic mu opioid receptor agonist with pharmacologic and analgesic properties similar to those of morphine. The principal actions of therapeutic value are analgesia or maintenance in opioid dependence. When methadone is administered for treatment of opioid dependence Available online at www.sciencedirect.com European Journal of Pharmacology 579 (2008) 160 – 166 www.elsevier.com/locate/ejphar ⁎ Corresponding author. National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing China. Tel.: +86 10 82802459; fax: +86 10 62032624. E-mail address: llu@bjmu.edu.cn (L. Lu). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.09.042