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Updated: May 17, 2026
Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
TACR1 genotypes predict fMRI response to alcohol cues and level of alcohol dependence
Sara Blaine1, Eric Claus, Nicole Harlaar
1Department of Psychology , University of Colorado, Boulder, Colorado 80309, USA. ra.blaine@colorado.edu
Background:
The tachykinin receptor 1 (TACR1) gene is a promising candidate gene in the search for the genetic basis of alcohol dependence (AD); TACR1 antagonists improve symptomology not only in preclinical models of AD but also in a clinical sample of detoxified alcoholics (George et al., Science 319:1536, 2008). The purpose of the current study was to determine whether TACR1 single nucleotide polymorphisms (SNPs) were associated with (i) blood oxygen level dependent (BOLD) activation in response to gustatory alcohol cues in a sample of heavy drinkers and (ii) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) AD symptom count in a large, publicly available data set-the Study of Addictions: Genetics and Environment Genome Wide Association study (SAGE GWAS) (Bierut et al., 2010).
Methods:
First, we examined relationships between TACR1 genotypes and neural responses during a craving task in 326 individuals with alcohol use disorders. Next, correlational analyses between 69 TACR1 SNPs and DSM-IV-TR AD symptoms were performed on the SAGE data set.
Results:
rs3771863, rs3755459, and rs1106855 predicted BOLD activation in response to alcohol cues in those same reward and reinforcement brain areas, especially in the medial prefrontal cortex, striatum, and insula. rs3771863 also predicted AD symptom count in the SAGE data set and BOLD activation in the mesocorticolimbic pathway response to alcohol cues.
Conclusions:
Each of the 5 SNPs in the TACR1 gene that was significantly related to AD severity in the SAGE data set and/or the BOLD response to the craving task is near the 3' or 5' areas of the gene and may therefore be near mutations with potential functional significance. In particular, the potential functional significance of rs1106855 should be explored because of its location within a stop codon.
Insights
Genetic variations in the tachykinin receptor 1 (TACR1) gene are linked to alcohol dependence (AD) symptoms and brain responses to alcohol cues. Specific TACR1 single nucleotide polymorphisms (SNPs) may influence neural activity and AD severity.
Area of Science:
- Neurogenetics
- Addiction Psychiatry
- Molecular Psychiatry
Background:
- The tachykinin receptor 1 (TACR1) gene is implicated in alcohol dependence (AD).
- TACR1 antagonists show therapeutic potential in preclinical and clinical AD models.
- Investigating TACR1 genetic variations is crucial for understanding AD's biological underpinnings.
Purpose of the Study:
- To investigate the association between TACR1 single nucleotide polymorphisms (SNPs) and brain activity (BOLD response) to alcohol cues in heavy drinkers.
- To examine the relationship between TACR1 SNPs and AD symptom severity using the Study of Addictions: Genetics and Environment Genome Wide Association study (SAGE GWAS) data.
Main Methods:
- Examined TACR1 genotypes and neural responses during an alcohol cue-induced craving task in 326 individuals with alcohol use disorders.
- Performed correlational analyses between 69 TACR1 SNPs and AD symptoms in the SAGE GWAS dataset.
Main Results:
- Specific TACR1 SNPs (rs3771863, rs3755459, rs1106855) predicted blood oxygen level dependent (BOLD) activation in brain reward areas (medial prefrontal cortex, striatum, insula) in response to alcohol cues.
- rs3771863 was also associated with AD symptom count and BOLD activation in the mesocorticolimbic pathway.
Conclusions:
- Several TACR1 SNPs, located near gene extremities, show potential functional significance in AD.
- rs1106855 warrants further investigation due to its location within a stop codon, suggesting a potential role in AD pathogenesis.
