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DRD2 Genotype-Based Variants Modulates D2 Receptor Distribution in Ventral Striatum.

Mikaeel Valli1,2,3, Sang Soo Cho1,2, Mario Masellis4

  • 1Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.

Molecular Neurobiology
|March 9, 2019
PubMed
Summary

Genetic variations in the DRD2 gene influence dopamine D2 receptor binding in the ventral striatum. This finding impacts our understanding of dopaminergic signaling in the brain.

Keywords:
DRD2 geneDopamine D2 receptorPositron emission tomographySingle nucleotide polymorphism[11C]-(+)-PHNO radiotracer

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Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Dopaminergic signaling in the striatum is vital for motor control and cognitive functions.
  • Two dopamine D2 receptor isoforms (D2 long and D2 short) are expressed in striatal neurons.
  • Single nucleotide polymorphisms (SNPs) rs2283265 and rs1076560 in the DRD2 gene affect D2 receptor expression levels.

Purpose of the Study:

  • To investigate how DRD2 gene polymorphisms (rs2283265) influence in vivo D2 receptor distribution within the nigrostriatal dopaminergic system.
  • To utilize Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO to assess D2 receptor binding in healthy young adults.

Main Methods:

  • Genotyping of 20 healthy young adults for the DRD2 rs2283265 SNP (CC, CA, AA genotypes).
  • PET imaging using the radiotracer [11C]-(+)-PHNO to measure D2 receptor binding potential.
  • Statistical analysis to compare [11C]-(+)-PHNO binding across different genotype groups in basal ganglia regions.

Main Results:

  • A significant effect of genotype on [11C]-(+)-PHNO binding was observed in the ventral striatum.
  • Individuals with CC and CA genotypes exhibited higher D2 receptor binding in the ventral striatum compared to AA genotype carriers.
  • No significant differences in D2 receptor binding were found among genotypes in other basal ganglia regions.

Conclusions:

  • Preliminary findings suggest that DRD2 gene polymorphisms influence dopaminergic signaling in the ventral striatum.
  • The observed genotype-dependent differences in binding may be attributed to variations in D2 receptor quantity, affinity, or both.
  • This research provides insights into the genetic modulation of dopamine D2 receptor availability in the human brain.