Dopamine transporter availability in alcohol and opioid dependent subjects - a ^99mTc-TRODAT-1SPECT imaging and genetic association study

Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n= 20 each of AD, OD and controls) were recruited. SPECT/CT imaging using Tc-99m-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 1 Orepeat and 9repeat alleles being the most common. The AD individuals with DAT1 promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the lOrepeat VNTR also showed reduced DAT availability. This is the first imaging study using Tc-99m-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 1 Orepeat individuals associated with decreased DAT availability in AD.