Dopamine transporter levels in cocaine dependent subjects

Abstract

Cocaine use is a significant problem in the US and it is well established that cocaine binds to the dopamine transporter (DAT) in the brain. This study was designed to determine if the DAT levels measured by 99mTc TRODAT SPECT (single photon emission computed tomography) brain scans are altered in cocaine dependent subjects and to explore clinical correlates of such alterations. SPECT brain scans were acquired on 21 cocaine dependent subjects and 21 healthy matched controls. There were significantly higher DAT levels in cocaine dependent subjects compared to controls for the anterior putamen (p=0.003; Cohen's d effect size=0.98), posterior putamen (p<0.001; effect size=1.32), and caudate (p=0.003; effect size=0.97). DAT levels in these regions were 10%, 17%, and 8% higher in the cocaine dependent subjects compared to controls. DAT levels were unrelated to craving, severity of cocaine use, or duration of cocaine use, but DAT levels in the caudate and anterior putamen were significantly (p<0.05) negatively correlated with days since last use of cocaine.

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

“…The two SPECT studies in cocaine users had durations of abstinence of a maximum of 4 days25 and mean of 7 days. 24 As such, residual cocaine could block radiotracer binding to DAT, resulting in a slight underestimation of DAT levels in these studies. The results of heterogeneity and sensitivity analysis are provided in supplementary material (figure 2).…”

“…The meta-analysis showed significantly reduced dopamine transporter availability in amphetamine-like stimulant users (effect size: −1.47 ([95% CI, −1.83 - −1.1], p<0.001). There were 5 studies in cocaine users 24–26,36,37. However, one study was excluded as it included cocaine users with potential CNS co-morbidity (HIV) 36.…”

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

“…Interestingly, recent data indicate that cocaine abuse, in contrast with METH/AMPH abuse, does not lead to PD (Curtin et al, 2015). Furthermore, other studies report increased DAT levels in striatal regions of recently abstinent cocaine users or postmortem cocaineabusing subjects, compared with control subjects (Mash et al, 2002;Crits-Christoph et al, 2008). In addition, DAT function as assessed by [ 3 H]DA uptake is elevated postmortem in cocaine-abusing subjects (Mash et al, 2002).…”

Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking

“…Cocaine dramatically increases DAT surface expression in mammals 34,41 , although the underlying molecular mechanisms remain elusive. There are two ways Vav2 may contribute to this process.…”