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Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals.
Chloe J Jordan1, Zheng-Xiong Xi2
1Division of Alcohol, Drugs and Addiction, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, United States.
Frontiers in Neuroscience
|January 31, 2022
Summary
Identifying genetic risk factors for substance use disorders (SUD) is crucial for developing effective treatments. Transgenic approaches show promise in pinpointing genes, like those for dopamine receptors, that increase vulnerability to drug addiction.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Substance use disorders (SUD) have significant environmental risk factors, but genetic vulnerabilities are less understood.
- Genome-Wide Association Studies (GWAS) have identified numerous gene variants but lack robust clinical validation.
- Transgenic approaches offer a promising avenue for identifying and validating SUD risk genes.
Purpose of the Study:
- To review recent advancements in identifying candidate genes for drug use and addiction using transgenic methods.
- To explore the hypothesis that reduced expression of specific genes increases susceptibility to drug use and addiction.
- To discuss the role of identified candidate genes in drug reward and addiction.
Main Methods:
- Review of literature on transgenic approaches for identifying SUD risk genes.
- Analysis of gene variants associated with increased drug self-administration or relapse in animal models.
- Examination of findings from gene-knockout mice and rats in addiction models.
Main Results:
- Several candidate genes, including those encoding dopamine D2 and D3 receptors, mGluR2, M4 muscarinic acetylcholine receptors, and α5 nicotinic acetylcholine receptors, were identified.
- Decreased expression of these genes appears to correlate with increased risk for drug use and addiction.
- Gene-knockout studies in animal models provide evidence for the role of these receptors in addiction.
Conclusions:
- Transgenic approaches are effective in identifying and validating genetic risk factors for SUD.
- Candidate genes affecting neurotransmitter receptors play a significant role in addiction vulnerability.
- Future research should focus on gene-based medication development for SUD treatment.
