The dopamine (DA) transporter DAT1 is a major target bound by cocaine in brain. We examined the influence of functional genetic variants in DAT1 on cocaine addiction. Repeat polymorphisms, including a 30-bp variable-number tandem repeat (VNTR) in intron 8 (Int8 VNTR) with two common alleles, were genotyped in cocaine-dependent abusers (n ‫؍‬ 699) and in controls with no past history of drug abuse (n ‫؍‬ 866) from Sã o Paulo, Brazil. Positive association was observed with allele 3 of the Int8 VNTR and cocaine abuse (allele odds ratio ‫؍‬ 1.2, 95% confidence interval ‫؍‬ 1.01-1.37, P ‫؍‬ 0.036; 3͞3 homozygote odds ratio ‫؍‬ 1.45, 95% confidence interval ‫؍‬ 1.18 -1.78, P ‫؍‬ 0.0008). Population stratification was assessed and did not affect the results. Haplotypic analyses using additional polymorphisms indicated that the Int8 VNTR is responsible for the observed association. Functional analyses in reportergene constructs, demonstrated that allele 3 mediates significant (P < 0.05) but small reduced expression compared with the ''protective'' allele 2. This difference increased when 1 and 10 M cocaine was added to the cell culture (Ϸ40% reduction of the 3 allele expression versus the 2 allele). The 3 allele also demonstrated Ϸ3-fold-increased expression over the 2 allele in response to KCl plus forskolin challenge. We demonstrate a robust association between cocaine dependence and a VNTR allele in SLC6A3, conferring a small but detectible effect, and we show that this VNTR may be functional. This study suggests that DAT1 gene variation may play a role in cocaine dependence etiology.addiction ͉ genetics ͉ SLC6A3

The Coronavirus Disease 2019 (COVID-19) pandemic has undoubtedly had a major impact on the provision of physical healthcare in Ireland and worldwide. The mental health impact of this pandemic cannot be underestimated, particularly relating to patients suffering from addiction. Heightened public stress and anxiety levels, increasing isolation and the physical consequences of addiction play a large role in the proliferation and ongoing relapse of substance misuse and behavioural addiction. Service provision is an ongoing challenge not only due to the increasing need for services given the increased mental health burden of COVID-19 but also the restrictions in place in clinical areas to achieve social distancing. The necessary adaptations to service provision provide opportunities for the analysis of current processes used in our addiction unit and the introduction of new processes to our service. The current crisis tests the sustainability of the service to provide the high standard of care required for these patients.

We find evidence, although modest, of a medium-sized effect of DAT1 genotype on the ability to stop smoking early in a smoking cessation attempt. If the effect is real, and is strongest in the very early stages of smoking cessation, this suggests that the primary utility of DAT1 screening in this field will be in the identification of those most at risk of early relapse after quitting.

This review assessed the evidence of an association between genotypes of the dopamine transporter (DAT1, SLC6A3) 3' untranslated region (3'UTR) variable number of tandem repeats (VNTR) and smoking cessation. Five studies (seven cohorts) comprising 2155 subjects were included in the meta-analysis. All gave data on the number of smokers who had stopped smoking and the number still smoking for those with one or more variant 9-repeat alleles and other genotypes. Three studies (comprising five cohorts) were cross-sectional population surveys and two were smoking cessation treatment programs with follow-up. Four of the five studies (six of the seven cohorts) showed a trend in favor of cessation when the variant 9-repeat allele was present, although only one study showed a statistically significant effect. The pooled odds ratio in favor of a greater likelihood of cessation for the variant 9-repeat allele was 1.15 [95% confidence interval (CI) = 0.97-1.37]. In a more refined analysis where cohorts within studies were treated as separate samples and adjusted odds ratios were used, the overall pooled odds ratio in favor of cessation with the 9-repeat alleles was 1.20 (95% CI = 1.01-1.43). These results support the hypothesis that the DAT1 3'UTR VNTR polymorphism is associated with smoking cessation. One or more variant 9-repeat alleles relative to the more common 10-repeat allele confers a greater likelihood of cessation, indicative of lower dependence on tobacco. The effect was a 20% increase in the odds of cessation for those with a variant allele.