Genetics Lab

Head: Dr. Mohammad Reza Zarrindast, Ph.D. of Pharmacology

Manager: Dr. Fatemeh Tirgar, Ph.D. of Neuroscience

Recent studies on behavior, neurobiology, and genetic of addiction at the National Center for Addiction Studies (INCAS) in Iran have aimed to identify and analyze the genetic factors influencing addiction and substance-related behaviors based on the scientific and practical needs of the country. The main research areas include:

1. Identification of Addiction-Related Genes

• Examination of genes that increase susceptibility to substance addiction. For instance, genes associated with the dopaminergic system, such asDRD2, COMT,andDAT1, which play a role in reward regulation and pleasure-seeking behaviors.
• Investigation of genes involved in drug metabolism, including those encoding enzymes such asCYP450, which influence drug breakdown in the body.
• Analysis of genetic variations in addiction and their association with brain disorders such as autism, depression, ADHD, and etc.

2. Epigenetic Studies in Addiction

• Assessment of environmental factors (such as stress, nutrition, and substance use) on epigenetic modifications (e.g., DNA methylation and histone acetylation) and their role in addictive behaviors.
• Examination of epigenetic changes resulting from chronic substance use and their association with treatment response.
• Investigation of transgenerational epigenetic effects of chronic substance use across second and third generations.

3. Neurobiology of the Reward System

1. • Analysis of neural pathways associated with the reward system of the brain, particularly the dopaminergic system, which plays a central role in addiction.
   • Investigation of the effects of substances on brain structure and function, including key regions such as:

Nucleus Accumbens: The primary center for reinforcement and pleasure.

Prefrontal Cortex: Associated with decision-making and impulse control.

Amygdala and Hippocampus: Involved in memory processing and emotional regulation.

4. Electrophysiological Studies on Key Addiction-Related Brain Regions

Examination of neuronal electrical activity changes using thesingle-unit recordingtechnique in the nucleus accumbens, prefrontal cortex, and amygdala.

5. Genetic Individual Differences in Addiction and Treatment Response & Biomarker Analysis

1. • Identification of addiction-related biomarkers, including genetic, proteomic, or metabolic markers.
   • Discovery of genetic biomarkers that can predict patient responses to pharmacological treatments (e.g., methadone, buprenorphine, and naltrexone).
   • Utilization of these biomarkers for early diagnosis, risk prediction, and treatment efficacy assessment.
   • Study of genetic polymorphisms influencing individual susceptibility to drugs and treatment outcomes.

6. Heritability of Addiction

1. • Research on family-based and twin populations to evaluate the role of genetic and environmental factors in addiction heritability.
   • Analysis of how gene-environment interactions can increase addiction risk.

7. NeuroGenetic Factors in Addiction to Different Substances

1. • Investigation of genetic and neurobiological differences in addiction to various substances (e.g., opium, methamphetamine, crack, alcohol, and nicotine).
   • Analysis of how specific genetic traits influence substance preference and dependence severity.

Prominent Behavioral and Genetic Addiction Projects at INCAS:

• International Collaborations: INCAS has engaged in collaborative projects with international universities to identify novel addiction-related genes.
• Epigenetic Research: Analysis of histone methylation in substance users and comparison with healthy individuals.
• Genetic Correlation Studies: Investigation of the relationship between genetic polymorphisms and behavioral disorders in substance-dependent individuals.
• Behavioral Studies: Examination of the effects of different substances and therapeutic interventions on laboratory animals, including assessments of depression, anxiety, locomotor activity, memory, and social interactions.

These studies significantly contribute to a deeper understanding of the biological mechanisms underlying addiction and can facilitate the development of personalized medicine and preventive strategies. These research areas not only address national priorities but also align with international commitments in drug control and management in Iran. As a leading research center, the INCAS genetics and neuroscience laboratories strives to provide scientific and practical solutions to combat addiction through interdisciplinary research and international collaboration.

Genetics Laboratory at INCAS:

The Genetics Laboratory at the National Center for Addiction Studies is equipped with:

• Western Blot Apparatus: To analyze protein expression changes.
• NanoDrop Spectrophotometer: To measure DNA concentrations.
• Real-Time PCR Machine: To evaluate gene expression changes.