Dopamine transporter availability in heroin-dependent subjects and controls: longitudinal changes during abstinence and the effects of Jitai tablets treatment

Abstract

These findings suggest that chronic heroin use induces long-lasting striatal DAT reductions. DAT availability remained unchanged during a 6-month period of abstinence. Treatment with Jitai appears to be effective at increasing striatal DAT availability.

Longitudinal changes of dopamine transporters in heroin users during abstinence

“…This right-greater-than-left asymmetry has been reported in previous studies where healthy people were found to have the right-greater-than-left asymmetry in D 2 receptor and DAT availability in the caudate (Laakso et al 2001;Tomer et al 2008). Moreover, several imaging studies in opioid or methamphetamine dependent subjects and healthy controls also found a slight right-great-than-left asymmetry in DAT levels in the striatum Liu et al 2013;Shi et al 2008;Yuan et al 2014). Nevertheless, no significant differences in these right-greater-than-left asymmetries were reported.…”

“…Previous clinical trials have documented the efficacy of JTT at inhibiting withdrawal symptoms and restoring the physiological functions altered by chronic drug use (Xu et al 2000;Zihong et al 2007). A prior study from our laboratory also documented that striatal DAT availability remained at reduced levels in heroin-dependent subjects during a 6-month period of abstinence, and treatment with JTT led to increased DAT after 6 months (Liu et al 2013). However, whether striatal DAT levels can be normalized after longer period of abstinence, and whether JTT treatment longer than 6 months could induce a further increase in DAT and improve neuropsychological functions remains unknown.…”

“…For example, two human postmortem studies found a modest DAT reduction in the nucleus accumbens but not in the striatum (Kish et al 2001), and a single-photon emission computed tomography (SPECT) imaging study found no association between long-term opioid exposure and reduced striatal DAT (Cosgrove et al 2010). More recent preclinical and clinical studies, however, have provided consistent evidence for reduced DAT levels in opioid addiction Jia et al 2005;Liang et al 2014;Liu et al 2013;Shi et al 2008;Yeh et al 2012).…”

“…Upon acute administration, opioid drugs of abuse activate brain dopaminergic neurons as evidenced by increased synaptic DA concentrations in the striatum (Dichiara and Imperato 1988;Rouge-Pont et al 2002). Chronic opiate use leads to a variety of compensatory changes, such as reductions in DA transporters (DAT), DA receptors, and synaptic DA levels (Kish et al 2001;Liu et al 2013;Wilson et al 1996). DAT is a key transmembrane protein that regulates DA reuptake from the synaptic cleft and is involved in the modulation of dopaminergic neurotransmission and the regulation of reward and dependence in drug addiction (Gainetdinov et al 1998;Volkow et al 1997).…”

“…To answer these questions, we designed this follow-up study as a time extension from our previous study (Liu et al 2013). SPECT imaging with [ 99m Tc]TRODAT-1 was used to assess DAT availability in detoxified heroin users and healthy controls.…”