Journal of Neural Transmission

, Volume 126, Issue 2, pp 193–199 | Cite as

Effects of DRD2 splicing-regulatory polymorphism and DRD4 48 bp VNTR on crack cocaine addiction

  • Anderson R. Stolf
  • Renata B. Cupertino
  • Diana Müller
  • Breno Sanvicente-Vieira
  • Tatiana Roman
  • Eduardo S. Vitola
  • Eugenio H. Grevet
  • Lisia von Diemen
  • Felix H. P. Kessler
  • Rodrigo Grassi-Oliveira
  • Claiton H. D. Bau
  • Diego L. Rovaris
  • Flavio Pechansky
  • Jaqueline B. SchuchEmail author
Psychiatry and Preclinical Psychiatric Studies - Original Article


There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formation of DRD2–DRD4 heteromers. The dopaminergic role on the vulnerability to addiction appears to be influenced by sex. A cross-sectional study with 307 crack cocaine addicts and 770 controls was conducted. The influence of DRD2 rs2283265 and DRD4 48 bp VNTR in exon 3 variants, as well as their interaction on crack cocaine addiction susceptibility and severity were evaluated in women and men separately. An association between the DRD2 T allele and crack cocaine addiction was found in women. In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction. No influence of DRD2 and DRD4 variants was observed in men regarding addiction severity. This study reinforces the role of dopaminergic genes in externalizing behaviors, especially the influence of DRD2–DRD4 interaction on SUD. This is the fourth sample that independently associated the DRD2–DRD4 interaction with SUD itself or related disorders. In addition, our findings point out to a potential difference of dopaminergic neurotransmission across sex influencing addiction susceptibility.


Cocaine Crack Dependence Dopamine receptor D2 Dopamine receptor D4 Substance use disorder 



We are thankful to the staff of the participating psychiatric units for all their support with data collection.


This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq, 476529/2012-3, 466722/2014-1, and 466802/2014-5) and Secretaria Nacional de Políticas sobre Drogas (SENAD, 82264/2015). The funding sources had no involvement in study design; collection, analyses, and interpretation of data; in the writing of the report; in the decision to submit the article for publication.

Compliance with ethical standards

Conflict of interest

The author(s) declare the following potential conflict of interest with respect to the research, authorship, and/or publication of this article: Dr. Grevet was on the speaker’s bureau for Novartis and Shire for the last 3 years. He also received travel awards (air tickets and hotel accommodations) for participating in two psychiatric meetings from Shire and Novartis. All other authors reported no financial interests or potential conflicts of interest.

Supplementary material

702_2018_1946_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 15 KB)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Anderson R. Stolf
    • 1
  • Renata B. Cupertino
    • 2
  • Diana Müller
    • 2
  • Breno Sanvicente-Vieira
    • 3
  • Tatiana Roman
    • 2
  • Eduardo S. Vitola
    • 4
  • Eugenio H. Grevet
    • 4
  • Lisia von Diemen
    • 1
  • Felix H. P. Kessler
    • 1
  • Rodrigo Grassi-Oliveira
    • 3
  • Claiton H. D. Bau
    • 1
    • 4
  • Diego L. Rovaris
    • 2
  • Flavio Pechansky
    • 1
  • Jaqueline B. Schuch
    • 2
    • 5
    Email author
  1. 1.Center for Drug and Alcohol Research, Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Department of Genetics, Instituto de BiociênciasUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Developmental Cognitive Neuroscience Lab (DCNL)Pontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.ADHD Outpatient Program, Adult DivisionHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  5. 5.Laboratory of Immunosenescence, Graduate Program in Biomedical GerontologyPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil

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